Proposed Molecular Beam Determination of Energy Partition in the Photodissociation of Polyatomic Molecules

DOE R&D Accomplishments Database

Zare, P. N.; Herschbach, D. R.

1964-01-29

Conventional photochemical experiments give no information about the partitioning of energy between translational recoil and internal excitation of the fragment molecules formed in photodissociation of a polyatomic molecule. In a molecular beam experiment, it becomes possible to determine the energy partition from the form of the laboratory angular distribution of one of the photodissociation products. A general kinematic analysis is worked out in detail, and the uncertainty introduced by the finite angular resolution of the apparatus and the velocity spread in the parent beam is examined. The experimental requirements are evaluated for he photolysis of methyl iodide by the 2537 angstrom Hg line.

Sensitivity and resolution in frequency comb spectroscopy of buffer gas cooled polyatomic molecules

NASA Astrophysics Data System (ADS)

Changala, P. Bryan; Spaun, Ben; Patterson, David; Doyle, John M.; Ye, Jun

2016-12-01

We discuss the use of cavity-enhanced direct frequency comb spectroscopy in the mid-infrared region with buffer gas cooling of polyatomic molecules for high-precision rovibrational absorption spectroscopy. A frequency comb coupled to an optical enhancement cavity allows us to collect high-resolution, broad-bandwidth infrared spectra of translationally and rotationally cold (10-20 K) gas-phase molecules with high absorption sensitivity and fast acquisition times. The design and performance of the combined apparatus are discussed in detail. Recorded rovibrational spectra in the CH stretching region of several organic molecules, including vinyl bromide (CH_2CHBr), adamantane (C_{10}H_{16}), and diamantane (C_{14}H_{20}) demonstrate the resolution and sensitivity of this technique, as well as the intrinsic challenges faced in extending the frontier of high-resolution spectroscopy to large complex molecules.

Rapid-Adiabatic Control of Ro-Vibrational Populations in Polyatomic Molecules

NASA Astrophysics Data System (ADS)

Zak, Emil J.; Yachmenev, Andrey

2017-06-01

We present a simple method for control of ro-vibrational populations in polyatomic molecules in the presence of inhomogeneous electric fields [1]. Cooling and trapping of heavy polar polyatomic molecules has become one of the frontier goals in high-resolution molecular spectroscopy, especially in the context of parity violation measurement in chiral compounds [2]. A key step toward reaching this goal would be development of a robust and efficient protocol for control of populations of ro-vibrational states in polyatomic, often floppy molecules. Here we demonstrate a modification of the stark-chirped rapid-adiabatic-passage technique (SCRAP) [3], designed for achieving high levels of control of ro-vibrational populations over a selected region in space. The new method employs inhomogeneous electric fields to generate space- and time- controlled Stark-shifts of energy levels in molecules. Adiabatic passage between ro-vibrational states is enabled by the pump pulse, which raises the value of the Rabi frequency. This Stark-chirped population transfer can be used in manipulation of population differences between high-field-seeking and low-field-seeking states of molecules in the Stark decelerator [4]. Appropriate timing of voltages on electric rods located along the decelerator combined with a single pump laser renders our method as potentially more efficient than traditional Stark decelerator techniques. Simulations for NH_3 show significant improvement in effectiveness of cooling, with respect to the standard 'moving-potential' method [5]. At the same time a high phase-space acceptance of the molecular packet is maintained. E. J. Zak, A. Yachmenev (submitted). C. Medcraft, R. Wolf, M. Schnell, Angew. Chem. Int. Ed., 53, 43, 11656-11659 (2014) M. Oberst, H. Munch, T. Halfman, PRL 99, 173001 (2007). K. Wohlfart, F. Grätz, F. Filsinger, H. Haak, G. Meijer, J. Küpper, Phys. Rev. A 77, 031404(R) (2008). H. L. Bethlem, F. M. H. Crompvoets, R. T. Jongma, S. Y. T. van de Meerakker, G. Meijer, Phys. Rev. A, 65, 053416 (2002).

Benchmark quality total atomization energies of small polyatomic molecules

NASA Astrophysics Data System (ADS)

Martin, Jan M. L.; Taylor, Peter R.

1997-05-01

Successive coupled-cluster [CCSD(T)] calculations in basis sets of spdf, spdfg, and spdfgh quality, combined with separate Schwartz-type extrapolations A+B/(l+1/2)α of the self-consistent field (SCF) and correlation energies, permit the calculations of molecular total atomization energies (TAEs) with a mean absolute error of as low as 0.12 kcal/mol. For the largest molecule treated, C2H4, we find ∑D0=532.0 kcal/mol, in perfect agreement with experiment. The aug-cc-pV5Z basis set recovers on average about 99% of the valence correlation contribution to the TAE, and essentially the entire SCF contribution.

Ion mobilities in diatomic gases: measurement versus prediction with non-specular scattering models.

PubMed

Larriba, Carlos; Hogan, Christopher J

2013-05-16

Ion/electrical mobility measurements of nanoparticles and polyatomic ions are typically linked to particle/ion physical properties through either application of the Stokes-Millikan relationship or comparison to mobilities predicted from polyatomic models, which assume that gas molecules scatter specularly and elastically from rigid structural models. However, there is a discrepancy between these approaches; when specular, elastic scattering models (i.e., elastic-hard-sphere scattering, EHSS) are applied to polyatomic models of nanometer-scale ions with finite-sized impinging gas molecules, predictions are in substantial disagreement with the Stokes-Millikan equation. To rectify this discrepancy, we developed and tested a new approach for mobility calculations using polyatomic models in which non-specular (diffuse) and inelastic gas-molecule scattering is considered. Two distinct semiempirical models of gas-molecule scattering from particle surfaces were considered. In the first, which has been traditionally invoked in the study of aerosol nanoparticles, 91% of collisions are diffuse and thermally accommodating, and 9% are specular and elastic. In the second, all collisions are considered to be diffuse and accommodating, but the average speed of the gas molecules reemitted from a particle surface is 8% lower than the mean thermal speed at the particle temperature. Both scattering models attempt to mimic exchange between translational, vibrational, and rotational modes of energy during collision, as would be expected during collision between a nonmonoatomic gas molecule and a nonfrozen particle surface. The mobility calculation procedure was applied considering both hard-sphere potentials between gas molecules and the atoms within a particle and the long-range ion-induced dipole (polarization) potential. Predictions were compared to previous measurements in air near room temperature of multiply charged poly(ethylene glycol) (PEG) ions, which range in morphology from compact to highly linear, and singly charged tetraalkylammonium cations. It was found that both non-specular, inelastic scattering rules lead to excellent agreement between predictions and experimental mobility measurements (within 5% of each other) and that polarization potentials must be considered to make correct predictions for high-mobility particles/ions. Conversely, traditional specular, elastic scattering models were found to substantially overestimate the mobilities of both types of ions.

Time-resolved photoelectron spectroscopy of polyatomic molecules using 42-nm vacuum ultraviolet laser based on high harmonics generation

NASA Astrophysics Data System (ADS)

Nishitani, Junichi; West, Christopher W.; Higashimura, Chika; Suzuki, Toshinori

2017-09-01

Time-resolved photoelectron spectroscopy (TRPES) of gaseous polyatomic molecules using 266-nm (4.7 eV) pump and 42-nm (29.5 eV) probe pulses is presented. A 1-kHz Ti:sapphire laser with a 35 fs pulse duration is employed to generate high harmonics in Kr gas, and the 19th harmonic (42-nm) was selected using two SiC/Mg mirrors. Clear observation of the ultrafast electronic dephasing in pyrazine and photoisomerization of 1,3-cyclohexadiene demonstrates the feasibility of TRPES with the UV pump and VUV probe pulses under weak excitation conditions in the perturbation regime.

Overset grid implementation of the complex Kohn variational method for electron-polyatomic molecule scattering

NASA Astrophysics Data System (ADS)

McCurdy, C. William; Lucchese, Robert L.; Greenman, Loren

2017-04-01

The complex Kohn variational method, which represents the continuum wave function in each channel using a combination of Gaussians and Bessel or Coulomb functions, has been successful in numerous applications to electron-polyatomic molecule scattering and molecular photoionization. The hybrid basis representation limits it to relatively low energies (< 50 eV) , requires an approximation to exchange matrix elements involving continuum functions, and hampers its coupling to modern electronic structure codes for the description of correlated target states. We describe a successful implementation of the method using completely adaptive overset grids to describe continuum functions, in which spherical subgrids are placed on every atomic center to complement a spherical master grid that describes the behavior at large distances. An accurate method for applying the free-particle Green's function on the grid eliminates the need to operate explicitly with the kinetic energy, enabling a rapidly convergent Arnoldi algorithm for solving linear equations on the grid, and no approximations to exchange operators are made. Results for electron scattering from several polyatomic molecules will be presented. Army Research Office, MURI, WN911NF-14-1-0383 and U. S. DOE DE-SC0012198 (at Texas A&M).

Enthalpic parameters of interaction between diglycylglycine and polyatomic alcohols in aqueous solutions

NASA Astrophysics Data System (ADS)

Mezhevoi, I. N.; Badelin, V. G.

2015-12-01

Integral enthalpies of solution Δsol H m of diglycylglycine in aqueous solutions of glycerol, ethylene glycol, and 1,2-propylene glycol are measured via solution calorimetry. The experimental data are used to calculate the standard enthalpies of solution (Δsol H°) and transfer (Δtr H°) of the tripeptide from water to aqueous solutions of polyatomic alcohols. The enthalpic pairwise coefficients h xy of interactions between the tripeptide and polyatomic alcohol molecules are calculated using the McMillan-Mayer solution theory and are found to have positive values. The findings are discussed using the theory of estimating various types of interactions in ternary systems and the effect the structural features of interacting biomolecules have on the thermochemical parameters of diglycylglycine dissolution.

Non-equilibrium effects of diatomic and polyatomic gases on the shock-vortex interaction based on the second-order constitutive model of the Boltzmann-Curtiss equation

NASA Astrophysics Data System (ADS)

Singh, S.; Karchani, A.; Myong, R. S.

2018-01-01

The rotational mode of molecules plays a critical role in the behavior of diatomic and polyatomic gases away from equilibrium. In order to investigate the essence of the non-equilibrium effects, the shock-vortex interaction problem was investigated by employing an explicit modal discontinuous Galerkin method. In particular, the first- and second-order constitutive models for diatomic and polyatomic gases derived rigorously from the Boltzmann-Curtiss kinetic equation were solved in conjunction with the physical conservation laws. As compared with a monatomic gas, the non-equilibrium effects result in a substantial change in flow fields in both macroscale and microscale shock-vortex interactions. Specifically, the computational results showed three major effects of diatomic and polyatomic gases on the shock-vortex interaction: (i) the generation of the third sound waves and additional reflected shock waves with strong and enlarged expansion, (ii) the dominance of viscous vorticity generation, and (iii) an increase in enstrophy with increasing bulk viscosity, related to the rotational mode of gas molecules. Moreover, it was shown that there is a significant discrepancy in flow fields between the microscale and macroscale shock-vortex interactions in diatomic and polyatomic gases. The quadrupolar acoustic wave source structures, which are typically observed in macroscale shock-vortex interactions, were not found in any microscale shock-vortex interactions. The physics of the shock-vortex interaction was also investigated in detail to examine vortex deformation and evolution dynamics over an incident shock wave. A comparative study of first- and second-order constitutive models was also conducted for the enstrophy and dissipation rate. Finally, the study was extended to the shock-vortex pair interaction case to examine the effects of pair interaction on vortex deformation and evolution dynamics.

Ion-momentum imaging of dissociative attachment of electrons to molecules

DOE Office of Scientific and Technical Information (OSTI.GOV)

Slaughter, D. S.; Belkacem, A.; McCurdy, C. W.

Here, we present an overview of experiments and theory relevant to dissociative electron attachment studied by momentum imaging. We describe several key examples of characteristic transient anion dynamics in the form of small polyatomic electron-molecule systems. In each of these examples the so-called axial recoil approximation is found to break down due to correlation of the electronic and nuclear degrees of freedom of the transient anion. Guided by anion fragment momentum measurements and predictions of the electron scattering attachment probability in the molecular frame, we demonstrate that accurate predictions of the dissociation dynamics can be achieved without a detailed investigationmore » of the surface topology of the relevant electronic states or the fragment trajectories on those surfaces.« less

Ion-momentum imaging of dissociative attachment of electrons to molecules

DOE PAGES

Slaughter, D. S.; Belkacem, A.; McCurdy, C. W.; ...

2016-10-24

Here, we present an overview of experiments and theory relevant to dissociative electron attachment studied by momentum imaging. We describe several key examples of characteristic transient anion dynamics in the form of small polyatomic electron-molecule systems. In each of these examples the so-called axial recoil approximation is found to break down due to correlation of the electronic and nuclear degrees of freedom of the transient anion. Guided by anion fragment momentum measurements and predictions of the electron scattering attachment probability in the molecular frame, we demonstrate that accurate predictions of the dissociation dynamics can be achieved without a detailed investigationmore » of the surface topology of the relevant electronic states or the fragment trajectories on those surfaces.« less

Recent advances in quantum scattering calculations on polyatomic bimolecular reactions.

PubMed

Fu, Bina; Shan, Xiao; Zhang, Dong H; Clary, David C

2017-12-11

This review surveys quantum scattering calculations on chemical reactions of polyatomic molecules in the gas phase published in the last ten years. These calculations are useful because they provide highly accurate information on the dynamics of chemical reactions which can be compared in detail with experimental results. They also serve as quantum mechanical benchmarks for testing approximate theories which can more readily be applied to more complicated reactions. This review includes theories for calculating quantities such as rate constants which have many important scientific applications.

Molecular extended thermodynamics of rarefied polyatomic gases and wave velocities for increasing number of moments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Arima, Takashi, E-mail: tks@stat.nitech.ac.jp; Mentrelli, Andrea, E-mail: andrea.mentrelli@unibo.it; Ruggeri, Tommaso, E-mail: tommaso.ruggeri@unibo.it

Molecular extended thermodynamics of rarefied polyatomic gases is characterized by two hierarchies of equations for moments of a suitable distribution function in which the internal degrees of freedom of a molecule is taken into account. On the basis of physical relevance the truncation orders of the two hierarchies are proven to be not independent on each other, and the closure procedures based on the maximum entropy principle (MEP) and on the entropy principle (EP) are proven to be equivalent. The characteristic velocities of the emerging hyperbolic system of differential equations are compared to those obtained for monatomic gases and themore » lower bound estimate for the maximum equilibrium characteristic velocity established for monatomic gases (characterized by only one hierarchy for moments with truncation order of moments N) by Boillat and Ruggeri (1997) (λ{sub (N)}{sup E,max})/(c{sub 0}) ⩾√(6/5 (N−1/2 )),(c{sub 0}=√(5/3 k/m T)) is proven to hold also for rarefied polyatomic gases independently from the degrees of freedom of a molecule. -- Highlights: •Molecular extended thermodynamics of rarefied polyatomic gases is studied. •The relation between two hierarchies of equations for moments is derived. •The equivalence of maximum entropy principle and entropy principle is proven. •The characteristic velocities are compared to those of monatomic gases. •The lower bound of the maximum characteristic velocity is estimated.« less

General features of the dissociative recombination of polyatomic molecules

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pratt, S. T.; Jungen, Ch.; Schneider, I. F.

We discuss some aspects of a simple expression for the low-energy dissociative recombination cross section that applies when the recombination process is dominated by the indirect mechanism. In most previous applications, this expression has been applied to capture into vibrationally excited Rydberg states with the assumption that capture is always followed by prompt dissociation. Here we consider the dissociative recombination of larger polyatomic ions and electrons. More specifically, we consider capture into electronically core-excited Rydberg states, and begin to assess its potential importance for larger systems.

General features of the dissociative recombination of polyatomic molecules

DOE PAGES

Pratt, S. T.; Jungen, Ch.; Schneider, I. F.; ...

2015-01-29

We discuss some aspects of a simple expression for the low-energy dissociative recombination cross section that applies when the recombination process is dominated by the indirect mechanism. In most previous applications, this expression has been applied to capture into vibrationally excited Rydberg states with the assumption that capture is always followed by prompt dissociation. Here we consider the dissociative recombination of larger polyatomic ions and electrons. More specifically, we consider capture into electronically core-excited Rydberg states, and begin to assess its potential importance for larger systems.

Crossed beam (E--VRT) energy transfer experiment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hertel, I.V.; Hofmann, H.; Rost, K.A.

A molecular crossed beam apparatus which has been developed to perform electronic-to-vibrational, rotational, translational (E--V,R,T) energy transfer studies is described. Its capabilities are illustrated on the basis of a number of energy transfer spectra obtained for collision systems of the type Na*+Mol(..nu..,j) ..-->..Na+Mol (..nu..',j') where Na* represents a laser excited sodium atom and Mol a diatomic or polyatomic molecule. Because of the lack of reliable dynamic theories on quenching processes, statistical approaches such as the ''linearly forced harmonic oscillator'' and ''prior distributions'' have been used to model the experimental spectra. The agreement is found to be satisfactory, so even suchmore » simple statistics may be useful to describe (E--V,R,T) energy transfer processes in collision systems with small molecules.« less

An exact variational method to calculate rovibrational spectra of polyatomic molecules with large amplitude motion

NASA Astrophysics Data System (ADS)

Yu, Hua-Gen

2016-08-01

We report a new full-dimensional variational algorithm to calculate rovibrational spectra of polyatomic molecules using an exact quantum mechanical Hamiltonian. The rovibrational Hamiltonian of system is derived in a set of orthogonal polyspherical coordinates in the body-fixed frame. It is expressed in an explicitly Hermitian form. The Hamiltonian has a universal formulation regardless of the choice of orthogonal polyspherical coordinates and the number of atoms in molecule, which is suitable for developing a general program to study the spectra of many polyatomic systems. An efficient coupled-state approach is also proposed to solve the eigenvalue problem of the Hamiltonian using a multi-layer Lanczos iterative diagonalization approach via a set of direct product basis set in three coordinate groups: radial coordinates, angular variables, and overall rotational angles. A simple set of symmetric top rotational functions is used for the overall rotation whereas a potential-optimized discrete variable representation method is employed in radial coordinates. A set of contracted vibrationally diabatic basis functions is adopted in internal angular variables. Those diabatic functions are first computed using a neural network iterative diagonalization method based on a reduced-dimension Hamiltonian but only once. The final rovibrational energies are computed using a modified Lanczos method for a given total angular momentum J, which is usually fast. Two numerical applications to CH4 and H2CO are given, together with a comparison with previous results.

An exact variational method to calculate rovibrational spectra of polyatomic molecules with large amplitude motion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu, Hua-Gen, E-mail: hgy@bnl.gov

We report a new full-dimensional variational algorithm to calculate rovibrational spectra of polyatomic molecules using an exact quantum mechanical Hamiltonian. The rovibrational Hamiltonian of system is derived in a set of orthogonal polyspherical coordinates in the body-fixed frame. It is expressed in an explicitly Hermitian form. The Hamiltonian has a universal formulation regardless of the choice of orthogonal polyspherical coordinates and the number of atoms in molecule, which is suitable for developing a general program to study the spectra of many polyatomic systems. An efficient coupled-state approach is also proposed to solve the eigenvalue problem of the Hamiltonian using amore » multi-layer Lanczos iterative diagonalization approach via a set of direct product basis set in three coordinate groups: radial coordinates, angular variables, and overall rotational angles. A simple set of symmetric top rotational functions is used for the overall rotation whereas a potential-optimized discrete variable representation method is employed in radial coordinates. A set of contracted vibrationally diabatic basis functions is adopted in internal angular variables. Those diabatic functions are first computed using a neural network iterative diagonalization method based on a reduced-dimension Hamiltonian but only once. The final rovibrational energies are computed using a modified Lanczos method for a given total angular momentum J, which is usually fast. Two numerical applications to CH{sub 4} and H{sub 2}CO are given, together with a comparison with previous results.« less

A systematic and feasible method for computing nuclear contributions to electrical properties of polyatomic molecules

NASA Astrophysics Data System (ADS)

Luis, Josep M.; Duran, Miquel; Andrés, José L.

1997-08-01

An analytic method to evaluate nuclear contributions to electrical properties of polyatomic molecules is presented. Such contributions control changes induced by an electric field on equilibrium geometry (nuclear relaxation contribution) and vibrational motion (vibrational contribution) of a molecular system. Expressions to compute the nuclear contributions have been derived from a power series expansion of the potential energy. These contributions to the electrical properties are given in terms of energy derivatives with respect to normal coordinates, electric field intensity or both. Only one calculation of such derivatives at the field-free equilibrium geometry is required. To show the useful efficiency of the analytical evaluation of electrical properties (the so-called AEEP method), results for calculations on water and pyridine at the SCF/TZ2P and the MP2/TZ2P levels of theory are reported. The results obtained are compared with previous theoretical calculations and with experimental values.

Polyatomic molecular Dirac-Hartree-Fock calculations with Gaussian basis sets

NASA Technical Reports Server (NTRS)

Dyall, Kenneth G.; Faegri, Knut, Jr.; Taylor, Peter R.

1990-01-01

Numerical methods have been used successfully in atomic Dirac-Hartree-Fock (DHF) calculations for many years. Some DHF calculations using numerical methods have been done on diatomic molecules, but while these serve a useful purpose for calibration, the computational effort in extending this approach to polyatomic molecules is prohibitive. An alternative more in line with traditional quantum chemistry is to use an analytical basis set expansion of the wave function. This approach fell into disrepute in the early 1980's due to problems with variational collapse and intruder states, but has recently been put on firm theoretical foundations. In particular, the problems of variational collapse are well understood, and prescriptions for avoiding the most serious failures have been developed. Consequently, it is now possible to develop reliable molecular programs using basis set methods. This paper describes such a program and reports results of test calculations to demonstrate the convergence and stability of the method.

High Resolution Studies of the Origins of Polyatomic Ions in Inductively Coupled Plasma-Mass Spectrometry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ferguson, Jill Wisnewski

2006-01-01

The inductively coupled plasma (ICP) is an atmospheric pressure ionization source. Traditionally, the plasma is sampled via a sampler cone. A supersonic jet develops behind the sampler, and this region is pumped down to a pressure of approximately one Torr. A skimmer cone is located inside this zone of silence to transmit ions into the mass spectrometer. The position of the sampler and skimmer cones relative to the initial radiation and normal analytical zones of the plasma is key to optimizing the useful analytical signal [1]. The ICP both atomizes and ionizes the sample. Polyatomic ions form through ion-molecule interactionsmore » either in the ICP or during ion extraction [l]. Common polyatomic ions that inhibit analysis include metal oxides (MO +), adducts with argon, the gas most commonly used to make up the plasma, and hydride species. While high resolution devices can separate many analytes from common interferences, this is done at great cost in ion transmission efficiency--a loss of 99% when using high versus low resolution on the same instrument [2]. Simple quadrupole devices, which make up the bulk of ICP-MS instruments in existence, do not present this option. Therefore, if the source of polyatomic interferences can be determined and then manipulated, this could potentially improve the figures of merit on all ICP-MS devices, not just the high resolution devices often utilized to study polyatomic interferences.« less

Vibrational Energy in Molecules and Nanoparticles: Applications to Energetic Materials

DTIC Science & Technology

2009-01-30

of vibrational energy in a polyatomic molecule, nitromethane . Work on water and amino acids partially supported by AFOSR are developmental in nature...have characterized the surface vibrations of HMX explosive and their interaction with polymer binders. We have introduced a major improvement in SFG...Vibrational energy in nitromethane and benzene E. Time resolved spectroscopy of chemistry in flash-heated nanoenergetic materials F. Complete

Earle K. Plyler Prize Lecture: The Three Pillars of Ultrafast Molecular Science - Time, Phase, Intensity

NASA Astrophysics Data System (ADS)

Stolow, Albert

We discuss the probing and control of molecular wavepacket dynamics in the context of three main `pillars' of light-matter interaction: time, phase, intensity. Time: Using short, coherent laser pulses and perturbative matter-field interactions, we study molecular wavepackets with a focus on the ultrafast non-Born-Oppenheimer dynamics, that is, the coupling of electronic and nuclear motions. Time-Resolved Photoelectron Spectroscopy (TRPES) is a powerful ultrafast probe of these processes in polyatomic molecules because it is sensitive both electronic and vibrational dynamics. Ideally, one would like to observe these ultrafast processes from the molecule's point of view - the Molecular Frame - thereby avoiding loss of information due to orientational averaging. This can be achieved by Time-Resolved Coincidence Imaging Spectroscopy (TRCIS) which images 3D recoil vectors of both photofragments and photoelectrons, in coincidence and as a function of time, permitting direct Molecular Frame imaging of valence electronic dynamics during a molecular dynamics. Phase: Using intermediate strength non-perturbative interactions, we apply the second order (polarizability) Non-Resonant Dynamic Stark Effect (NRDSE) to control molecular dynamics without any net absorption of light. NRDSE is also the interaction underlying molecular alignment and applies to field-free 1D of linear molecules and field-free 3D alignment of general (asymmetric) molecules. Using laser alignment, we can transiently fix a molecule in space, yielding a more general approach to direct Molecular Frame imaging of valence electronic dynamics during a chemical reaction. Intensity: In strong (ionizing) laser fields, a new laser-matter physics emerges for polyatomic systems wherein both the single active electron picture and the adiabatic electron response, both implicit in the standard 3-step models, can fail dramatically. This has important consequences for all attosecond strong field spectroscopies of polyatomic molecules, including high harmonic generation (HHG). We discuss an experimental method, Channel-Resolved Above Threshold Ionization (CRATI), which directly unveils the electronic channels participating in the attosecond molecular strong field ionization response [10]. This work was supported by the National Research Council of Canada and the Natural Sciences & Engineering Research Council.

Extension of the MIRS computer package for the modeling of molecular spectra: From effective to full ab initio ro-vibrational Hamiltonians in irreducible tensor form

NASA Astrophysics Data System (ADS)

Nikitin, A. V.; Rey, M.; Champion, J. P.; Tyuterev, Vl. G.

2012-07-01

The MIRS software for the modeling of ro-vibrational spectra of polyatomic molecules was considerably extended and improved. The original version [Nikitin AV, Champion JP, Tyuterev VlG. The MIRS computer package for modeling the rovibrational spectra of polyatomic molecules. J Quant Spectrosc Radiat Transf 2003;82:239-49.] was especially designed for separate or simultaneous treatments of complex band systems of polyatomic molecules. It was set up in the frame of effective polyad models by using algorithms based on advanced group theory algebra to take full account of symmetry properties. It has been successfully used for predictions and data fitting (positions and intensities) of numerous spectra of symmetric and spherical top molecules within the vibration extrapolation scheme. The new version offers more advanced possibilities for spectra calculations and modeling by getting rid of several previous limitations particularly for the size of polyads and the number of tensors involved. It allows dealing with overlapping polyads and includes more efficient and faster algorithms for the calculation of coefficients related to molecular symmetry properties (6C, 9C and 12C symbols for C3v, Td, and Oh point groups) and for better convergence of least-square-fit iterations as well. The new version is not limited to polyad effective models. It also allows direct predictions using full ab initio ro-vibrational normal mode Hamiltonians converted into the irreducible tensor form. Illustrative examples on CH3D, CH4, CH3Cl, CH3F and PH3 are reported reflecting the present status of data available. It is written in C++ for standard PC computer operating under Windows. The full package including on-line documentation and recent data are freely available at http://www.iao.ru/mirs/mirs.htm or http://xeon.univ-reims.fr/Mirs/ or http://icb.u-bourgogne.fr/OMR/SMA/SHTDS/MIRS.html and as supplementary data from the online version of the article.

Electron Interactions with Non-Linear Polyatomic Molecules and Their Radicals

DTIC Science & Technology

1993-12-01

developed which generates SCE quantities from molecular wave functions. This progress was realized in terms of some actual calculations on some molecules...section 4.A describes the basics of the Partial Differential Equation Theory; section 4.B describes the generalization to a finite element...Information Service (NTIS). At NTIS, it will be available to the general public, including foreign nations. This technical report has been reviewed and

Molecular-beam Studies of Primary Photochemical Processes

DOE R&D Accomplishments Database

Lee, Y. T.

1982-12-01

Application of the method of molecular-beam photofragmentation translational spectroscopy to the investigation of primary photochemical processes of polyatomic molecules is described. Examples will be given to illustrate how information concerning the energetics, dynamics, and mechanism of dissociation processes can be obtained from the precise measurements of angular and velocity distributions of products in an experiment in which a well-defined beam of molecules is crossed with a laser.

Matrix-enhanced secondary ion mass spectrometry: The Alchemist's solution?

NASA Astrophysics Data System (ADS)

Delcorte, Arnaud

2006-07-01

Because of the requirements of large molecule characterization and high-lateral resolution SIMS imaging, the possibility of improving molecular ion yields by the use of specific sample preparation procedures has recently generated a renewed interest in the static SIMS community. In comparison with polyatomic projectiles, however, signal enhancement by a matrix might appear to some as the alchemist's versus the scientist's solution to the current problems of organic SIMS. In this contribution, I would like to discuss critically the pros and cons of matrix-enhanced SIMS procedures, in the new framework that includes polyatomic ion bombardment. This discussion is based on a short review of the experimental and theoretical developments achieved in the last decade with respect to the three following approaches: (i) blending the analyte with a low-molecular weight organic matrix (MALDI-type preparation procedure); (ii) mixing alkali/noble metal salts with the analyte; (iii) evaporating a noble metal layer on the analyte sample surface (organic molecules, polymers).

Dual chain perturbation theory: A new equation of state for polyatomic molecules

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marshall, Bennett D., E-mail: bennett.d.marshall@exxonmobil.com

In the development of equations of state for polyatomic molecules, thermodynamic perturbation theory (TPT) is widely used to calculate the change in free energy due to chain formation. TPT is a simplification of a more general and exact multi-density cluster expansion for associating fluids. In TPT, all contributions to the cluster expansion which contain chain–chain interactions are neglected. That is, all inter-chain interactions are treated at the reference fluid level. This allows for the summation of the cluster theory in terms of reference system correlation functions only. The resulting theory has been shown to be accurate and has been widelymore » employed as the basis of many engineering equations of state. While highly successful, TPT has many handicaps which result from the neglect of chain–chain contributions. The subject of this document is to move beyond the limitations of TPT and include chain–chain contributions to the equation of state.« less

Multi-layer Lanczos iteration approach to calculations of vibrational energies and dipole transition intensities for polyatomic molecules

DOE PAGES

Yu, Hua-Gen

2015-01-28

We report a rigorous full dimensional quantum dynamics algorithm, the multi-layer Lanczos method, for computing vibrational energies and dipole transition intensities of polyatomic molecules without any dynamics approximation. The multi-layer Lanczos method is developed by using a few advanced techniques including the guided spectral transform Lanczos method, multi-layer Lanczos iteration approach, recursive residue generation method, and dipole-wavefunction contraction. The quantum molecular Hamiltonian at the total angular momentum J = 0 is represented in a set of orthogonal polyspherical coordinates so that the large amplitude motions of vibrations are naturally described. In particular, the algorithm is general and problem-independent. An applicationmore » is illustrated by calculating the infrared vibrational dipole transition spectrum of CH₄ based on the ab initio T8 potential energy surface of Schwenke and Partridge and the low-order truncated ab initio dipole moment surfaces of Yurchenko and co-workers. A comparison with experiments is made. The algorithm is also applicable for Raman polarizability active spectra.« less

Experimental and Theoretical Studies of Interstellar Grains. Ph.D. Thesis - Maryland Univ., College Park, 1982

NASA Technical Reports Server (NTRS)

Nuth, J. A., III

1981-01-01

Steady state vibrational populations of SiO and CO in dilute black body radiation fields were calculated as a function of total pressure, kinetic temperature and chemical composition of the gas. Approximate calculations for polyatomic molecules are presented. Vibrational disequilibrium becomes increasingly significant as total pressure and radiation density decrease. Many regions of postulated grain formation are found to be far from thermal equilibrium before the onset of nucleation. Calculations based upon classical nucleation theory or equilibrium thermodynamics are expected to be of dubious value in such regions. Laboratory measurements of the extinction of small iron and magnetite grains were made from 195 nm to 830 nm and found to be consistent with predictions based upon published optical constants. This implies that small iron particles are not responsible for the 220 nm interstellar extinction features. Additional measurements are discussed.

Determination of molecular spectroscopic parameters and energy-transfer rates by double-resonance spectroscopy

NASA Technical Reports Server (NTRS)

Steinfeld, J. I.; Foy, B.; Hetzler, J.; Flannery, C.; Klaassen, J.; Mizugai, Y.; Coy, S.

1990-01-01

The spectroscopy of small to medium-size polyatomic molecules can be extremely complex, especially in higher-lying overtone and combination vibrational levels. The high density of levels also complicates the understanding of inelastic collision processes, which is required to model energy transfer and collision broadening of spectral lines. Both of these problems can be addressed by double-resonance spectroscopy, i.e., time-resolved pump-probe measurements using microwave, infrared, near-infrared, and visible-wavelength sources. Information on excited-state spectroscopy, transition moments, inelastic energy transfer rates and propensity rules, and pressure-broadening parameters may be obtained from such experiments. Examples are given for several species of importance in planetary atmospheres, including ozone, silane, ethane, and ammonia.

HIGH RESOLUTION SPECTROSCOPY IN THE GAS PHASE: Even Large Molecules Have Well-Defined Shapes

NASA Astrophysics Data System (ADS)

Pratt, David W.

1998-10-01

A review of recent high-resolution microwave, infrared, and optical spectroscopy experiments demonstrates that remarkable progress has been made in the past 20 years in determining the equilibrium geometries of large polyatomic molecules and their clusters in the gas phase, and how these geometries change when the photon is absorbed. A special focus is on the dynamical information that can be obtained from such studies, particularly of electronically excited states.

Time-Dependent Wave Packet Dynamics Calculations of Cross Sections for Ultracold Scattering of Molecules

NASA Astrophysics Data System (ADS)

Huang, Jiayu; Liu, Shu; Zhang, Dong H.; Krems, Roman V.

2018-04-01

Because the de Broglie wavelength of ultracold molecules is very large, the cross sections for collisions of molecules at ultracold temperatures are always computed by the time-independent quantum scattering approach. Here, we report the first accurate time-dependent wave packet dynamics calculation for reactive scattering of ultracold molecules. Wave packet dynamics calculations can be applied to molecular systems with more dimensions and provide real-time information on the process of bond rearrangement and/or energy exchange in molecular collisions. Our work thus makes possible the extension of rigorous quantum calculations of ultracold reaction properties to polyatomic molecules and adds a new powerful tool for the study of ultracold chemistry.

Time-Dependent Wave Packet Dynamics Calculations of Cross Sections for Ultracold Scattering of Molecules.

PubMed

Huang, Jiayu; Liu, Shu; Zhang, Dong H; Krems, Roman V

2018-04-06

Because the de Broglie wavelength of ultracold molecules is very large, the cross sections for collisions of molecules at ultracold temperatures are always computed by the time-independent quantum scattering approach. Here, we report the first accurate time-dependent wave packet dynamics calculation for reactive scattering of ultracold molecules. Wave packet dynamics calculations can be applied to molecular systems with more dimensions and provide real-time information on the process of bond rearrangement and/or energy exchange in molecular collisions. Our work thus makes possible the extension of rigorous quantum calculations of ultracold reaction properties to polyatomic molecules and adds a new powerful tool for the study of ultracold chemistry.

Stabilizing potentials in bound state analytic continuation methods for electronic resonances in polyatomic molecules

DOE PAGES

White, Alec F.; Head-Gordon, Martin; McCurdy, C. William

2017-01-30

The computation of Siegert energies by analytic continuation of bound state energies has recently been applied to shape resonances in polyatomic molecules by several authors. Here, we critically evaluate a recently proposed analytic continuation method based on low order (type III) Padé approximants as well as an analytic continuation method based on high order (type II) Padé approximants. We compare three classes of stabilizing potentials: Coulomb potentials, Gaussian potentials, and attenuated Coulomb potentials. These methods are applied to a model potential where the correct answer is known exactly and to the 2Π g shape resonance of N 2 - whichmore » has been studied extensively by other methods. Both the choice of stabilizing potential and method of analytic continuation prove to be important to the accuracy of the results. We then conclude that an attenuated Coulomb potential is the most effective of the three for bound state analytic continuation methods. With the proper potential, such methods show promise for algorithmic determination of the positions and widths of molecular shape resonances.« less

Variational treatment of electron-polyatomic-molecule scattering calculations using adaptive overset grids

NASA Astrophysics Data System (ADS)

Greenman, Loren; Lucchese, Robert R.; McCurdy, C. William

2017-11-01

The complex Kohn variational method for electron-polyatomic-molecule scattering is formulated using an overset-grid representation of the scattering wave function. The overset grid consists of a central grid and multiple dense atom-centered subgrids that allow the simultaneous spherical expansions of the wave function about multiple centers. Scattering boundary conditions are enforced by using a basis formed by the repeated application of the free-particle Green's function and potential Ĝ0+V ̂ on the overset grid in a Born-Arnoldi solution of the working equations. The theory is shown to be equivalent to a specific Padé approximant to the T matrix and has rapid convergence properties, in both the number of numerical basis functions employed and the number of partial waves employed in the spherical expansions. The method is demonstrated in calculations on methane and CF4 in the static-exchange approximation and compared in detail with calculations performed with the numerical Schwinger variational approach based on single-center expansions. An efficient procedure for operating with the free-particle Green's function and exchange operators (to which no approximation is made) is also described.

Stabilizing potentials in bound state analytic continuation methods for electronic resonances in polyatomic molecules

DOE Office of Scientific and Technical Information (OSTI.GOV)

White, Alec F.; Head-Gordon, Martin; McCurdy, C. William

The computation of Siegert energies by analytic continuation of bound state energies has recently been applied to shape resonances in polyatomic molecules by several authors. Here, we critically evaluate a recently proposed analytic continuation method based on low order (type III) Padé approximants as well as an analytic continuation method based on high order (type II) Padé approximants. We compare three classes of stabilizing potentials: Coulomb potentials, Gaussian potentials, and attenuated Coulomb potentials. These methods are applied to a model potential where the correct answer is known exactly and to the 2Π g shape resonance of N 2 - whichmore » has been studied extensively by other methods. Both the choice of stabilizing potential and method of analytic continuation prove to be important to the accuracy of the results. We then conclude that an attenuated Coulomb potential is the most effective of the three for bound state analytic continuation methods. With the proper potential, such methods show promise for algorithmic determination of the positions and widths of molecular shape resonances.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhai, Liangjun; Zheng, Yujun, E-mail: yzheng@sdu.edu.cn

In the present study, the dynamical behaviors of tripartite entanglement of vibrations in triatomic molecules are studied based on the Lie algebraic models of molecules. The dynamical behaviors of tripartite entanglement of the local mode molecule H{sub 2}O and normal mode molecule NO{sub 2} are comparatively studied for different initial states by employing the general concurrence. Our results show that the dynamics of tripartite entanglement are relied on the dynamics of intramolecular energy distribution. The local mode molecule is more suitable to construct the tripartite entangled states. Also, the greater degree of tripartite entanglement can be obtained if the stretchingmore » vibration is first excited. These results shed new light on the understanding of quantum multipartite entanglement of vibrations in the polyatomic molecules.« less

Evaporation of Lennard-Jones fluids.

PubMed

Cheng, Shengfeng; Lechman, Jeremy B; Plimpton, Steven J; Grest, Gary S

2011-06-14

Evaporation and condensation at a liquid/vapor interface are ubiquitous interphase mass and energy transfer phenomena that are still not well understood. We have carried out large scale molecular dynamics simulations of Lennard-Jones (LJ) fluids composed of monomers, dimers, or trimers to investigate these processes with molecular detail. For LJ monomers in contact with a vacuum, the evaporation rate is found to be very high with significant evaporative cooling and an accompanying density gradient in the liquid domain near the liquid/vapor interface. Increasing the chain length to just dimers significantly reduces the evaporation rate. We confirm that mechanical equilibrium plays a key role in determining the evaporation rate and the density and temperature profiles across the liquid/vapor interface. The velocity distributions of evaporated molecules and the evaporation and condensation coefficients are measured and compared to the predictions of an existing model based on kinetic theory of gases. Our results indicate that for both monatomic and polyatomic molecules, the evaporation and condensation coefficients are equal when systems are not far from equilibrium and smaller than one, and decrease with increasing temperature. For the same reduced temperature T/T(c), where T(c) is the critical temperature, these two coefficients are higher for LJ dimers and trimers than for monomers, in contrast to the traditional viewpoint that they are close to unity for monatomic molecules and decrease for polyatomic molecules. Furthermore, data for the two coefficients collapse onto a master curve when plotted against a translational length ratio between the liquid and vapor phase.

Interstellar H3+

PubMed Central

Oka, Takeshi

2006-01-01

Protonated molecular hydrogen, H3+, is the simplest polyatomic molecule. It is the most abundantly produced interstellar molecule, next only to H2, although its steady state concentration is low because of its extremely high chemical reactivity. H3+ is a strong acid (proton donor) and initiates chains of ion-molecule reactions in interstellar space thus leading to formation of complex molecules. Here, I summarize the understandings on this fundamental species in interstellar space obtained from our infrared observations since its discovery in 1996 and discuss the recent observations and analyses of H3+ in the Central Molecular Zone near the Galatic center that led to a revelation of a vast amount of warm and diffuse gas existing in the region. PMID:16894171

Potential energy surfaces and reaction dynamics of polyatomic molecules

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chang, Yan-Tyng

A simple empirical valence bond (EVB) model approach is suggested for constructing global potential energy surfaces for reactions of polyatomic molecular systems. This approach produces smooth and continuous potential surfaces which can be directly utilized in a dynamical study. Two types of reactions are of special interest, the unimolecular dissociation and the unimolecular isomerization. For the first type, the molecular dissociation dynamics of formaldehyde on the ground electronic surface is investigated through classical trajectory calculations on EVB surfaces. The product state distributions and vector correlations obtained from this study suggest very similar behaviors seen in the experiments. The intramolecular hydrogenmore » atom transfer in the formic acid dimer is an example of the isomerization reaction. High level ab initio quantum chemistry calculations are performed to obtain optimized equilibrium and transition state dimer geometries and also the harmonic frequencies.« less

Ultrafast electron dynamics in phenylalanine initiated by attosecond pulses.

PubMed

Calegari, F; Ayuso, D; Trabattoni, A; Belshaw, L; De Camillis, S; Anumula, S; Frassetto, F; Poletto, L; Palacios, A; Decleva, P; Greenwood, J B; Martín, F; Nisoli, M

2014-10-17

In the past decade, attosecond technology has opened up the investigation of ultrafast electronic processes in atoms, simple molecules, and solids. Here, we report the application of isolated attosecond pulses to prompt ionization of the amino acid phenylalanine and the subsequent detection of ultrafast dynamics on a sub-4.5-femtosecond temporal scale, which is shorter than the vibrational response of the molecule. The ability to initiate and observe such electronic dynamics in polyatomic molecules represents a crucial step forward in attosecond science, which is progressively moving toward the investigation of more and more complex systems. Copyright © 2014, American Association for the Advancement of Science.

Metal atom oxidation laser

DOEpatents

Jensen, R.J.; Rice, W.W.; Beattie, W.H.

1975-10-28

A chemical laser which operates by formation of metal or carbon atoms and reaction of such atoms with a gaseous oxidizer in an optical resonant cavity is described. The lasing species are diatomic or polyatomic in nature and are readily produced by exchange or other abstraction reactions between the metal or carbon atoms and the oxidizer. The lasing molecules may be metal or carbon monohalides or monoxides.

Visualization of Potential Energy Function Using an Isoenergy Approach and 3D Prototyping

ERIC Educational Resources Information Center

Teplukhin, Alexander; Babikov, Dmitri

2015-01-01

In our three-dimensional world, one can plot, see, and comprehend a function of two variables at most, V(x,y). One cannot plot a function of three or more variables. For this reason, visualization of the potential energy function in its full dimensionality is impossible even for the smallest polyatomic molecules, such as triatomics. This creates…

Hydrated proton and hydroxide charge transfer at the liquid/vapor interface of water

DOE Office of Scientific and Technical Information (OSTI.GOV)

Soniat, Marielle; Rick, Steven W., E-mail: srick@uno.edu; Kumar, Revati

2015-07-28

The role of the solvated excess proton and hydroxide ions in interfacial properties is an interesting scientific question with applications in a variety of aqueous behaviors. The role that charge transfer (CT) plays in interfacial behavior is also an unsettled question. Quantum calculations are carried out on clusters of water with an excess proton or a missing proton (hydroxide) to determine their CT. The quantum results are applied to analysis of multi-state empirical valence bond trajectories. The polyatomic nature of the solvated excess proton and hydroxide ion results in directionally dependent CT, depending on whether a water molecule is amore » hydrogen bond donor or acceptor in relation to the ion. With polyatomic molecules, CT also depends on the intramolecular bond distances in addition to intermolecular distances. The hydrated proton and hydroxide affect water’s liquid/vapor interface in a manner similar to monatomic ions, in that they induce a hydrogen-bonding imbalance at the surface, which results in charged surface waters. This hydrogen bond imbalance, and thus the charged waters at the surface, persists until the ion is at least 10 Å away from the interface.« less

Optimal control of the population dynamics of the ground vibrational state of a polyatomic molecule

NASA Astrophysics Data System (ADS)

de Clercq, Ludwig E.; Botha, Lourens R.; Rohwer, Erich G.; Uys, Hermann; Du Plessis, Anton

2011-03-01

Simulating coherent control with femtosecond pulses on a polyatomic molecule with anharmonic splitting was demonstrated. The simulation mimicked pulse shaping of a Spatial Light Modulator (SLM) and the interaction was described with the Von Neumann equation. A transform limited pulse with a fluence of 600 J/m2 produced 18% of the population in an arbitrarily chosen upper vibrational state, n =2. Phase only and amplitude only shaped pulse produced optimum values of 60% and 40% respectively, of the population in the vibrational state, n=2, after interaction with the ultra short pulse. The combination of phase and amplitude shaping produced the best results, 80% of the population was in the targeted vibrational state, n=2, after interaction. These simulations were carried out with all the population initially in the ground vibrational level. It was found that even at room temperatures (300 Kelvin) that the population in the selected level is comparable with the case where all population is initially in the ground vibrational state. With a 10% noise added to the amplitude and phase masks, selective excitation of the targeted vibrational state is still possible.

Reduction of polyatomic interferences in ICP-MS by collision/reaction cell (CRC-ICP-MS) techniques

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eiden, Greg C; Barinaga, Charles J; Koppenaal, David W

2012-05-01

Polyatomic and other spectral interferences in plasma source mass spectrometry (PSMS) can be dramatically reduced using collision and reaction cells (CRC). These devices have been used for decades in fundamental studies of ion-molecule chemistry, but have only recently been applied to PSMS. Benefits of this approach as applied in inductively coupled plasma MS (ICP-MS) include interference reduction, isobar separation, and thermalization/focusing of ions. Novel ion-molecule chemistry schemes are now routinely designed and empirically evaluated with relative ease. These “chemical resolution” techniques can avert interferences requiring mass spectral resolutions of >600,000 (m/m). Purely physical ion beam processes, including collisional dampening andmore » collisional dissociation, are also employed to provide improved sensitivity, resolution, and spectral simplicity. CRC techniques are now firmly entrenched in current-day ICP-MS technology, enabling unprecedented flexibility and freedom from many spectral interferences. A significant body of applications has now been reported in the literature. CRC techniques are found to be most useful for specialized or difficult analytical needs and situations, and are employed in both single- and multi-element determination modes.« less

2012 Gordon Research Conference on Vibrational Spectroscopy - Formal Schedule and Speaker/Poster Program

DOE Office of Scientific and Technical Information (OSTI.GOV)

Geiger, Franz

2012-08-10

The Vibrational Spectroscopy conference brings together experimentalists and theoreticians working at the frontiers of modern vibrational spectroscopy, with a special emphasis on spectroscopies that probe the structure and dynamics of molecules in gases, liquids, and at interfaces. The conference explores the wide range of state-of-the-art techniques based on vibrational motion. These techniques span the fields of time-domain, high-resolution frequency-domain, spatially-resolved, nonlinear, and multidimensional spectroscopies. The conference highlights both the application of these techniques in chemistry, materials, biology, the environment, and medicine as well as the development of theoretical models that enable one to connect spectroscopic signatures to underlying molecular motionsmore » including chemical reaction dynamics. The conference goal is to advance the field of vibrational spectroscopy by bringing together a collection of researchers who share common interests and who will gain from discussing work at the forefront of several connected areas. The intent is to emphasize the insights and understanding that studies of vibrations provide about a variety of molecular systems ranging from small polyatomic molecules to large biomolecules, nanomaterials, and environmental systems.« less

Fit Point-Wise AB Initio Calculation Potential Energies to a Multi-Dimension Long-Range Model

NASA Astrophysics Data System (ADS)

Zhai, Yu; Li, Hui; Le Roy, Robert J.

2016-06-01

A potential energy surface (PES) is a fundamental tool and source of understanding for theoretical spectroscopy and for dynamical simulations. Making correct assignments for high-resolution rovibrational spectra of floppy polyatomic and van der Waals molecules often relies heavily on predictions generated from a high quality ab initio potential energy surface. Moreover, having an effective analytic model to represent such surfaces can be as important as the ab initio results themselves. For the one-dimensional potentials of diatomic molecules, the most successful such model to date is arguably the ``Morse/Long-Range'' (MLR) function developed by R. J. Le Roy and coworkers. It is very flexible, is everywhere differentiable to all orders. It incorporates correct predicted long-range behaviour, extrapolates sensibly at both large and small distances, and two of its defining parameters are always the physically meaningful well depth {D}_e and equilibrium distance r_e. Extensions of this model, called the Multi-Dimension Morse/Long-Range (MD-MLR) function, linear molecule-linear molecule systems and atom-non-linear molecule system. have been applied successfully to atom-plus-linear molecule, linear molecule-linear molecule and atom-non-linear molecule systems. However, there are several technical challenges faced in modelling the interactions of general molecule-molecule systems, such as the absence of radial minima for some relative alignments, difficulties in fitting short-range potential energies, and challenges in determining relative-orientation dependent long-range coefficients. This talk will illustrate some of these challenges and describe our ongoing work in addressing them. Mol. Phys. 105, 663 (2007); J. Chem. Phys. 131, 204309 (2009); Mol. Phys. 109, 435 (2011). Phys. Chem. Chem. Phys. 10, 4128 (2008); J. Chem. Phys. 130, 144305 (2009) J. Chem. Phys. 132, 214309 (2010) J. Chem. Phys. 140, 214309 (2010)

Polyad quantum numbers and multiple resonances in anharmonic vibrational studies of polyatomic molecules

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krasnoshchekov, Sergey V.; Stepanov, Nikolay F.

2013-11-14

In the theory of anharmonic vibrations of a polyatomic molecule, mixing the zero-order vibrational states due to cubic, quartic and higher-order terms in the potential energy expansion leads to the appearance of more-or-less isolated blocks of states (also called polyads), connected through multiple resonances. Such polyads of states can be characterized by a common secondary integer quantum number. This polyad quantum number is defined as a linear combination of the zero-order vibrational quantum numbers, attributed to normal modes, multiplied by non-negative integer polyad coefficients, which are subject to definition for any particular molecule. According to Kellman's method [J. Chem. Phys.more » 93, 6630 (1990)], the corresponding formalism can be conveniently described using vector algebra. In the present work, a systematic consideration of polyad quantum numbers is given in the framework of the canonical Van Vleck perturbation theory (CVPT) and its numerical-analytic operator implementation for reducing the Hamiltonian to the quasi-diagonal form, earlier developed by the authors. It is shown that CVPT provides a convenient method for the systematic identification of essential resonances and the definition of a polyad quantum number. The method presented is generally suitable for molecules of significant size and complexity, as illustrated by several examples of molecules up to six atoms. The polyad quantum number technique is very useful for assembling comprehensive basis sets for the matrix representation of the Hamiltonian after removal of all non-resonance terms by CVPT. In addition, the classification of anharmonic energy levels according to their polyad quantum numbers provides an additional means for the interpretation of observed vibrational spectra.« less

Application of the R-matrix method to photoionization of molecules.

PubMed

Tashiro, Motomichi

2010-04-07

The R-matrix method has been used for theoretical calculation of electron collision with atoms and molecules for long years. The method was also formulated to treat photoionization process, however, its application has been mostly limited to photoionization of atoms. In this work, we implement the R-matrix method to treat molecular photoionization problem based on the UK R-matrix codes. This method can be used for diatomic as well as polyatomic molecules, with multiconfigurational description for electronic states of both target neutral molecule and product molecular ion. Test calculations were performed for valence electron photoionization of nitrogen (N(2)) as well as nitric oxide (NO) molecules. Calculated photoionization cross sections and asymmetry parameters agree reasonably well with the available experimental results, suggesting usefulness of the method for molecular photoionization.

Simplified model to describe the dissociative recombination of linear polyatomic ions of astrophysical interest

NASA Astrophysics Data System (ADS)

Fonseca Dos Santos, Samantha; Douguet, Nicolas; Kokoouline, Viatcheslav; Orel, Ann

2013-05-01

We will present theoretical results on the dissociative recombination (DR) of the linear polyatomic ions HCNH+, HCO+ and N2H+. Besides their astrophysical importance, they also share the characteristic that at low electronic impact energies their DR process happens via the indirect DR mechanism. We apply a general simplified model successfully implemented to treat the DR process of the highly symmetric non-linear molecules H3+, CH3+, H3O+ and NH4+ to calculated cross sections and DR rates for these ions. The model is based on multichannel quantum defect theory and accounts for all the main ingredients of indirect DR. New perspectives on dissociative recombination of HCO+ will also be discussed, including the possible role of HOC+ in storage ring experimental results. This work is supported by the DOE Office of Basic Energy Science and the National Science Foundation, Grant No's PHY-11-60611 and PHY-10-68785.

Metal atom oxidation laser

DOEpatents

Jensen, R.J.; Rice, W.W.; Beattie, W.H.

1975-10-28

A chemical laser which operates by formation of metal or carbon atoms and reaction of such atoms with a gaseous oxidizer in an optical resonant cavity is described. The lasing species are diatomic or polyatomic in nature and are readily produced by exchange or other abstraction reactions between the metal or carbon atoms and the oxidizer. The lasing molecules may be metal or carbon monohalides or monoxides. (auth)

Astronomical chemistry.

PubMed

Klemperer, William

2011-01-01

The discovery of polar polyatomic molecules in higher-density regions of the interstellar medium by means of their rotational emission detected by radioastronomy has changed our conception of the universe from essentially atomic to highly molecular. We discuss models for molecule formation, emphasizing the general lack of thermodynamic equilibrium. Detailed chemical kinetics is needed to understand molecule formation as well as destruction. Ion molecule reactions appear to be an important class for the generally low temperatures of the interstellar medium. The need for the intrinsically high-quality factor of rotational transitions to definitively pin down molecular emitters has been well established by radioastronomy. The observation of abundant molecular ions both positive and, as recently observed, negative provides benchmarks for chemical kinetic schemes. Of considerable importance in guiding our understanding of astronomical chemistry is the fact that the larger molecules (with more than five atoms) are all organic.

Physics with Cold Molecules Using Buffer Gas Cooling: Precision Measurement, Collisions, and Laser Cooling

NASA Astrophysics Data System (ADS)

Hutzler, Nicholas R.; Doyle, John M.

2014-06-01

Cryogenic buffer gas cooled beams and cells can be used to study many species, from atoms and polar molecules to biomolecules. We report on recent applications of this technique to improve the limit on the electron electric dipole moment [1], load polar molecules into a magnetic trap through optical pumping [2], perform chirally sensitive microwave spectroscopy on polyatomic molecules [3], progress towards magneto-optical trapping of polar molecules [4], and studies of atom-molecule sticking [5]. [1] The ACME Collaboration: J. Baron et al., Science 343, p. 269 (2014) [2] B. Hemmerling et al., arXiv:1310.2669, to appear in Phys. Rev. Lett. [3] D. Patterson, M. Schnell, & J. M. Doyle, Nature 497, p. 475 (2013) [4] H. Lu et al., arXiv:1310.3239, to appear in New. J. Phys. [5] J. Piskorski et al., under preparation

Research Directed at Developing a Classical Theory to Describe Isotope Separation of Polyatomic Molecules Illuminated by Intense Infrared Radiation. Final Report for period May 7, 1979 to September 30, 1979; Extension December 31, 1997

DOE R&D Accomplishments Database

Lamb, W. E. Jr.

1981-12-01

This final report describes research on the theory of isotope separation produced by the illumination of polyatomic molecules by intense infrared laser radiation. This process is investigated by treating the molecule, sulfur hexafluoride, as a system of seven classical particles that obey the Newtonian equations of motion. A minicomputer is used to integrate these differential equations. The particles are acted on by interatomic forces, and by the time-dependent electric field of the laser. We have a very satisfactory expression for the interaction of the laser and the molecule which is compatible with infrared absorption and spectroscopic data. The interatomic potential is capable of improvement, and progress on this problem is still being made. We have made several computer runs of the dynamical behavior of the molecule using a reasonably good model for the interatomic force law. For the laser parameters chosen, we find that typically the molecule passes quickly through the resonance region into the quasi-continuum and even well into the real continuum before dissociation actually occurs. When viewed on a display terminal, the motions are exceedingly complex. As an aid to the visualization of the process, we have made a number of 16 mm movies depicting a three-dimensional representation of the motion of the seven particles. These show even more clearly the enormous complexity of the motions, and make clear the desirability of finding ways of characterizing the motion in simple ways without giving all of the numerical detail. One of the ways to do this is to introduce statistical parameters such as a temperature associated with the distribution of kinetic energies of the single particle. We have made such an analysis of our data runs, and have found favorable indications that such methods will prove useful in keeping track of the dynamical histories.

An On-the-Fly Surface-Hopping Program JADE for Nonadiabatic Molecular Dynamics of Polyatomic Systems: Implementation and Applications.

PubMed

Du, Likai; Lan, Zhenggang

2015-04-14

Nonadiabatic dynamics simulations have rapidly become an indispensable tool for understanding ultrafast photochemical processes in complex systems. Here, we present our recently developed on-the-fly nonadiabatic dynamics package, JADE, which allows researchers to perform nonadiabatic excited-state dynamics simulations of polyatomic systems at an all-atomic level. The nonadiabatic dynamics is based on Tully's surface-hopping approach. Currently, several electronic structure methods (CIS, TDHF, TDDFT(RPA/TDA), and ADC(2)) are supported, especially TDDFT, aiming at performing nonadiabatic dynamics on medium- to large-sized molecules. The JADE package has been interfaced with several quantum chemistry codes, including Turbomole, Gaussian, and Gamess (US). To consider environmental effects, the Langevin dynamics was introduced as an easy-to-use scheme into the standard surface-hopping dynamics. The JADE package is mainly written in Fortran for greater numerical performance and Python for flexible interface construction, with the intent of providing open-source, easy-to-use, well-modularized, and intuitive software in the field of simulations of photochemical and photophysical processes. To illustrate the possible applications of the JADE package, we present a few applications of excited-state dynamics for various polyatomic systems, such as the methaniminium cation, fullerene (C20), p-dimethylaminobenzonitrile (DMABN) and its primary amino derivative aminobenzonitrile (ABN), and 10-hydroxybenzo[h]quinoline (10-HBQ).

Polyatomic ions from a high current ion implanter driven by a liquid metal ion source.

PubMed

Pilz, W; Laufer, P; Tajmar, M; Böttger, R; Bischoff, L

2017-12-01

High current liquid metal ion sources are well known and found their first application as field emission electric propulsion thrusters in space technology. The aim of this work is the adaption of such kind of sources in broad ion beam technology. Surface patterning based on self-organized nano-structures on, e.g., semiconductor materials formed by heavy mono- or polyatomic ion irradiation from liquid metal (alloy) ion sources (LMAISs) is a very promising technique. LMAISs are nearly the only type of sources delivering polyatomic ions from about half of the periodic table elements. To overcome the lack of only very small treated areas by applying a focused ion beam equipped with such sources, the technology taken from space propulsion systems was transferred into a large single-end ion implanter. The main component is an ion beam injector based on high current LMAISs combined with suited ion optics allocating ion currents in the μA range in a nearly parallel beam of a few mm in diameter. Different types of LMAIS (needle, porous emitter, and capillary) are presented and characterized. The ion beam injector design is specified as well as the implementation of this module into a 200 kV high current ion implanter operating at the HZDR Ion Beam Center. Finally, the obtained results of large area surface modification of Ge using polyatomic Bi 2 + ions at room temperature from a GaBi capillary LMAIS will be presented and discussed.

Polyatomic ions from a high current ion implanter driven by a liquid metal ion source

NASA Astrophysics Data System (ADS)

Pilz, W.; Laufer, P.; Tajmar, M.; Böttger, R.; Bischoff, L.

2017-12-01

High current liquid metal ion sources are well known and found their first application as field emission electric propulsion thrusters in space technology. The aim of this work is the adaption of such kind of sources in broad ion beam technology. Surface patterning based on self-organized nano-structures on, e.g., semiconductor materials formed by heavy mono- or polyatomic ion irradiation from liquid metal (alloy) ion sources (LMAISs) is a very promising technique. LMAISs are nearly the only type of sources delivering polyatomic ions from about half of the periodic table elements. To overcome the lack of only very small treated areas by applying a focused ion beam equipped with such sources, the technology taken from space propulsion systems was transferred into a large single-end ion implanter. The main component is an ion beam injector based on high current LMAISs combined with suited ion optics allocating ion currents in the μA range in a nearly parallel beam of a few mm in diameter. Different types of LMAIS (needle, porous emitter, and capillary) are presented and characterized. The ion beam injector design is specified as well as the implementation of this module into a 200 kV high current ion implanter operating at the HZDR Ion Beam Center. Finally, the obtained results of large area surface modification of Ge using polyatomic Bi2+ ions at room temperature from a GaBi capillary LMAIS will be presented and discussed.

Coherent Bichromatic Force Deflection of Molecules

NASA Astrophysics Data System (ADS)

Kozyryev, Ivan; Baum, Louis; Aldridge, Leland; Yu, Phelan; Eyler, Edward E.; Doyle, John M.

2018-02-01

We demonstrate the effect of the coherent optical bichromatic force on a molecule, the polar free radical strontium monohydroxide (SrOH). A dual-frequency retroreflected laser beam addressing the X˜2Σ+↔A˜2Π1 /2 electronic transition coherently imparts momentum onto a cryogenic beam of SrOH. This directional photon exchange creates a bichromatic force that transversely deflects the molecules. By adjusting the relative phase between the forward and counterpropagating laser beams we reverse the direction of the applied force. A momentum transfer of 70 ℏk is achieved with minimal loss of molecules to dark states. Modeling of the bichromatic force is performed via direct numerical solution of the time-dependent density matrix and is compared with experimental observations. Our results open the door to further coherent manipulation of molecular motion, including the efficient optical deceleration of diatomic and polyatomic molecules with complex level structures.

Dynamics of pulsed expansion of polyatomic gas cloud: Internal-translational energy transfer contribution

NASA Astrophysics Data System (ADS)

Morozov, A. A.

2007-08-01

Polyatomic gas cloud expansion under pulsed laser evaporation is studied on the basis of one-dimensional direct Monte Carlo simulation. The effect of rotational-translational (RT) and vibrational-translational (VT) energy transfer on dynamics of the cloud expansion is considered. Efficiency of VT energy transfer dependence on the amount of evaporated matter is discussed. To analyze VT energy transfer impact, the number of collisions per molecule during the expansion is calculated. The data are generally in good agreement with available analytical and numerical predictions. Dependencies of the effective number of vibrational degrees of freedom on the number of vibrationally inelastic collisions are obtained and generalized. The importance of the consideration of energy transfer from the internal degrees of freedom to the translational ones is illustrated by an example of pulsed laser evaporation of polytetrafluoroethylene (PTFE). Based on the obtained regularities, analysis of experimental data on pulsed laser evaporation of aniline is performed. The calculated aniline vibrational temperature correlates well with the experimentally measured one.

POTENTIOLOGY (noun): study focusing on the development of new interatomic pair potential forms; sometimes pursued in an obsessive compulsive manner [The New Yorel Dictionary (2002, unpublished)].} IN SPECTROSCOPY: IT MATTERS

NASA Astrophysics Data System (ADS)

Le Roy, Robert J.

2009-06-01

Spectroscopists have long attempted to summarize what they know about small molecules in terms of a knowledge of potential energy curves or surfaces. For most of the past century, this involved deducing polynomial-expansion force-field coefficients from energy level expressions fitted to experimental data, or for diatomic molecules, by generating tables of many-digit RKR turning points from such expressions. In recent years, however, it has become increasingly common either to use high-level ab initio calculations to compute the desired potentials, or to determine parametrized global analytic potential functions from direct fits to spectroscopic data. In the former case, this invoked a need for robust, flexible, compact, and `portable' analytic potentials for summarizing the information contained in the (sometimes very large numbers of) ab initio points, and making them `user friendly'. In the latter case, the same properties are required for potentials used in the least-squares fitting procedure. In both cases, there is also a cardinal need for potential function forms that extrapolate sensibly, beyond the range of the experimental data or ab initio points. This talk will describe some recent developments in this area, and make a case for what is arguably the `best' general-purpose analytic potential function form now available. Applications to both diatomic molecules and simple polyatomic molecules will be discussed. footnote

Gaussian process model for extrapolation of scattering observables for complex molecules: From benzene to benzonitrile

NASA Astrophysics Data System (ADS)

Cui, Jie; Li, Zhiying; Krems, Roman V.

2015-10-01

We consider a problem of extrapolating the collision properties of a large polyatomic molecule A-H to make predictions of the dynamical properties for another molecule related to A-H by the substitution of the H atom with a small molecular group X, without explicitly computing the potential energy surface for A-X. We assume that the effect of the -H →-X substitution is embodied in a multidimensional function with unknown parameters characterizing the change of the potential energy surface. We propose to apply the Gaussian Process model to determine the dependence of the dynamical observables on the unknown parameters. This can be used to produce an interval of the observable values which corresponds to physical variations of the potential parameters. We show that the Gaussian Process model combined with classical trajectory calculations can be used to obtain the dependence of the cross sections for collisions of C6H5CN with He on the unknown parameters describing the interaction of the He atom with the CN fragment of the molecule. The unknown parameters are then varied within physically reasonable ranges to produce a prediction uncertainty of the cross sections. The results are normalized to the cross sections for He — C6H6 collisions obtained from quantum scattering calculations in order to provide a prediction interval of the thermally averaged cross sections for collisions of C6H5CN with He.

Rotational dynamics of polyatomic ions in aqueous solutions: From continuum model to mode-coupling theory, aided by computer simulations.

PubMed

Banerjee, Puja; Bagchi, Biman

2018-06-14

Due to the presence of the rotational mode and the distributed surface charges, the dynamical behavior of polyatomic ions in water differs considerably from those of the monatomic ions. However, their fascinating dynamical properties have drawn scant attention. We carry out theoretical and computational studies of a series of well-known polyatomic ions, namely, sulfate, nitrate, and acetate ions. All three ions exhibit different rotational diffusivity, with that of the nitrate ion being considerably larger than the other two. They all defy the hydrodynamic laws of size dependence. Study of the local structure around the ions provides valuable insight into the origin of these differences. We carry out a detailed study of the rotational diffusion of these ions by extensive computer simulation and by using the theoretical approaches of the dielectric friction developed by Fatuzzo-Mason (FM) and Nee-Zwanzig (NZ), and subsequently generalized by Alavi and Waldeck. A critical element of the FM-NZ theory is the decomposition of the total rotational friction, ζ Rot , into Stokes and dielectric parts. The study shows a dominant role of dielectric friction in the sense that if the ions are made neutral, the nature of diffusion changes and the values become much larger. Our analyses further reveal that the decomposition of total friction into the Stokes and dielectric friction breaks down for sulfate ions but remains semi-quantitatively valid for nitrate and acetate ions. We discuss the relationship between translational and rotational dielectric friction on rigid spherical ions. We develop a self-consistent mode-coupling theory (SC-MCT) formalism that could provide a unified view of rotational friction of polyatomic ions in polar medium. Our SC-MCT shows that the breakdown can be attributed to the change in the microscopic structural features. The mode-coupling theory helps in elucidating the role of coupling between translational and rotational motion of these ions. In fact, these two motions self-consistently determine the value of each other. The reference interaction site model-based MCT suggests an interesting relation between the torque-torque and the force-force time correlation function with the proportionality constant being determined by the geometry and the charge distribution of the polyatomic molecule. We point out several parallelisms between the theories of translational and rotation friction calculations of ions in polar liquids.

THE DYNAMICS OF HYDROGEN ATOM ABSTRACTION FROM POLYATOMIC MOLECULES.

DOE Office of Scientific and Technical Information (OSTI.GOV)

LIU,X.; SUITS,A.G.

2002-11-21

The hydrogen atom abstraction reaction is an important fundamental process that is extensively involved in atmospheric and combustion chemistry. The practical significance of this type of reaction with polyatomic hydrocarbons is manifest, which has led to many kinetics studies. The detailed understanding of these reactions requires corresponding dynamics studies. However, in comparison to the A + HX {radical} AH + X reactions, the study of the dynamics of A + HR {yields} AH + R reactions is much more difficult, both experimentally and theoretically (here and in the following, A stands for an atom, X stands for a halogen atom,more » and R stands for a polyatomic hydrocarbon radical). The complication stems from the structured R, in contrast to the structureless X. First of all, there are many internal degrees of freedom in R that can participate in the reaction. In addition, there are different carbon sites from which an H atom can be abstracted, and the dynamics are correspondingly different; there are also multiple identical carbon sites in HR and in the picture of a local reaction, there exist competitions between neighboring H atoms, and so on. Despite this complexity, there have been continuing efforts to obtain insight into the dynamics of these reactions. In this chapter, some examples are presented, including the reactions of ground state H, Cl, and O atoms, with particular focus on our recent work using imaging to obtain the differential cross sections for these reactions.« less

Use of a single trajectory to study product energy partitioning in unimolecular dissociation: mass effects for halogenated alkanes.

PubMed

Sun, Lipeng; Park, Kyoyeon; Song, Kihyung; Setser, Donald W; Hase, William L

2006-02-14

A single trajectory (ST) direct dynamics approach is compared with quasiclassical trajectory (QCT) direct dynamics calculations for determining product energy partitioning in unimolecular dissociation. Three comparisons are made by simulating C(2)H(5)F-->HF + C(2)H(4) product energy partitioning for the MP26-31G(*) and MP26-311 + + G(**) potential energy surfaces (PESs) and using the MP26-31G(*) PES for C(2)H(5)F dissociation as a model to simulate CHCl(2)CCl(3)-->HCl + C(2)Cl(4) dissociation and its product energy partitioning. The trajectories are initiated at the transition state with fixed energy in reaction-coordinate translation E(t) (double dagger). The QCT simulations have zero-point energy (ZPE) in the vibrational modes orthogonal to the reaction coordinate, while there is no ZPE for the STs. A semiquantitative agreement is obtained between the ST and QCT average percent product energy partitionings. The ST approach is used to study mass effects for product energy partitioning in HX(X = F or Cl) elimination from halogenated alkanes by using the MP26-31G(*) PES for C(2)H(5)F dissociation and varying the masses of the C, H, and F atoms. There is, at most, only a small mass effect for partitioning of energy to HX vibration and rotation. In contrast, there are substantial mass effects for partitioning to relative translation and the polyatomic product's vibration and rotation. If the center of mass of the polyatomic product is located away from the C atom from which HX recoils, the polyatomic has substantial rotation energy. Polyatomic products, with heavy atoms such as Cl atoms replacing the H atoms, receive substantial vibration energy that is primarily transferred to the wag-bend motions. For E(t) (double dagger) of 1.0 kcalmol, the ST calculations give average percent partitionings to relative translation, polyatomic vibration, polyatomic rotation, HX vibration, and HX rotation of 74.9%, 6.8%, 1.5%, 14.4%, and 2.4% for C(2)H(5)F dissociation and 39.7%, 38.1%, 0.2%, 16.1%, and 5.9% for a model of CHCl(2)CCl(3) dissociation.

Using quantum dynamics simulations to follow the competition between charge migration and charge transfer in polyatomic molecules

NASA Astrophysics Data System (ADS)

Spinlove, K. E.; Vacher, M.; Bearpark, M.; Robb, M. A.; Worth, G. A.

2017-01-01

Recent work, particularly by Cederbaum and co-workers, has identified the phenomenon of charge migration, whereby charge flow occurs over a static molecular framework after the creation of an electronic wavepacket. In a real molecule, this charge migration competes with charge transfer, whereby the nuclear motion also results in the re-distribution of charge. To study this competition, quantum dynamics simulations need to be performed. To break the exponential scaling of standard grid-based algorithms, approximate methods need to be developed that are efficient yet able to follow the coupled electronic-nuclear motion of these systems. Using a simple model Hamiltonian based on the ionisation of the allene molecule, the performance of different methods based on Gaussian Wavepackets is demonstrated.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cui, Jie; Krems, Roman V.; Li, Zhiying

We use classical trajectory calculations to study the effects of the interaction strength and the geometry of rigid polyatomic molecules on the formation of long-lived collision complexes at low collision energies. We first compare the results of the calculations for collisions of benzene molecules with rare gas atoms He, Ne, Ar, Kr, and Xe. The comparison illustrates that the mean lifetimes of the collision complexes increase monotonically with the strength of the atom–molecule interaction. We then compare the results of the atom–benzene calculations with those for benzene–benzene collisions. The comparison illustrates that the mean lifetimes of the benzene–benzene collision complexesmore » are significantly reduced due to non-ergodic effects prohibiting the molecules from sampling the entire configuration space. We find that the thermally averaged lifetimes of the benzene–benzene collisions are much shorter than those for Xe with benzene and similar to those for Ne with benzene.« less

Interstellar molecules - Origin by catalytic reactions on grain surfaces. [compound distribution analysis

NASA Technical Reports Server (NTRS)

Anders, E.; Hayatsu, R.; Studier, M. H.

1974-01-01

To determine the compound distribution formed by surface catalysis, mixtures of CO, D2, and ND2 were heated with nickel-iron or montmorillonite clay catalysts for 49-214 hours at 250 to 300 C. Compounds identified include most of the known polyatomic interstellar molecules, as well as homologous series of acetylenes, dienes, alcohols, aldehydes, ketones, ethers, esters, nitriles, amines, etc., and cyclic compounds such as furans and pyrroles. These homologous series are uniquely characteristic of surface catalysis. A search for the heavier members of these series, predicted to occur at 1/10th to 1/1,000th the abundance of the lightest members, thus comprises a crucial test of this mechanism.

Chirp effects on impulsive vibrational spectroscopy: a multimode perspective.

PubMed

Wand, Amir; Kallush, Shimshon; Shoshanim, Ofir; Bismuth, Oshrat; Kosloff, Ronnie; Ruhman, Sanford

2010-03-07

The well-documented propensity of negatively-chirped pulses to enhance resonant impulsive Raman scattering has been rationalized in terms of a one pulse pump-dump sequence which "follows" the evolution of the excited molecules and dumps them back at highly displaced configurations. The aim of this study was to extend the understanding of this effect to molecules with many displaced vibrational modes in the presence of condensed surroundings. In particular, to define an optimally chirped pulse, to investigate what exactly it "follows" and to discover how this depends on the molecule under study. To this end, linear chirp effects on vibrational coherences in poly-atomics are investigated experimentally and theoretically. Chirped pump-impulsive probe experiments are reported for Sulforhodamine-B ("Kiton Red"), Betaine-30 and Oxazine-1 in ethanol solutions with <10 fs resolution. Numerical simulations, including numerous displaced modes and electronic dephasing, are conducted to reproduce experimental results. Through semi-quantitative reproduction of experimental results in all three systems we show that the effect of group velocity dispersion (GVD) on the buildup of ground state wave-packets depends on the pulse spectrum, on the displacements of vibrational modes upon excitation, on the detuning of the excitation pulses from resonance, and on electronic dephasing rates. Akin to scenarios described for frequency-domain resonance Raman, within the small-displacement regime each mode responds to excitation chirp independently and the optimal GVD is mode-specific. Highly-displaced modes entangle the dynamics of excitation in different modes, requiring a multi-dimensional description of the response. Rapid photochemistry and ultrafast electronic dephasing narrow the window of opportunity for coherent manipulations, leading to a reduced and similar optimal chirp for different modes. Finally, non-intuitive coherent aspects of chirp "following" are predicted in the small-displacement and slow-dephasing regime, which remain to be observed in experiment.

Implementation of polyatomic MCTDHF capability

NASA Astrophysics Data System (ADS)

Haxton, Daniel; Jones, Jeremiah; Rescigno, Thomas; McCurdy, C. William; Ibrahim, Khaled; Williams, Sam; Vecharynski, Eugene; Rouet, Francois-Henry; Li, Xiaoye; Yang, Chao

2015-05-01

The implementation of the Multiconfiguration Time-Dependent Hartree-Fock method for poly- atomic molecules using a cartesian product grid of sinc basis functions will be discussed. The focus will be on two key components of the method: first, the use of a resolution-of-the-identity approximation; sec- ond, the use of established techniques for triple Toeplitz matrix algebra using fast Fourier transform over distributed memory architectures (MPI 3D FFT). The scaling of two-electron matrix element transformations is converted from O(N4) to O(N log N) by including these components. Here N = n3, with n the number of points on a side. We test the prelim- inary implementation by calculating absorption spectra of small hydro- carbons, using approximately 16-512 points on a side. This work is supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences, under the Early Career program, and by the offices of BES and Advanced Scientific Computing Research, under the SciDAC program.

Ultrasensitive detection of atmospheric trace gases using frequency modulation spectroscopy

NASA Technical Reports Server (NTRS)

Cooper, David E.

1986-01-01

Frequency modulation (FM) spectroscopy is a new technique that promises to significantly extend the state-of-the-art in point detection of atmospheric trace gases. FM spectroscopy is essentially a balanced bridge optical heterodyne approach in which a small optical absorption or dispersion from an atomic or molecular species of interest generates an easily detected radio frequency (RF) signal. This signal can be monitored using standard RF signal processing techniques and is, in principle, limited only by the shot noise generated in the photodetector by the laser source employed. The use of very high modulation frequencies which exceed the spectral width of the probed absorption line distinguishes this technique from the well-known derivative spectroscopy which makes use of low (kHz) modulation frequencies. FM spectroscopy was recently extended to the 10 micron infrared (IR) spectral region where numerous polyatomic molecules exhibit characteristic vibrational-rotational bands. In conjunction with tunable semiconductor diode lasers, the quantum-noise-limited sensitivity of the technique should allow for the detection of absorptions as small as .00000001 in the IR spectral region. This sensitivity would allow for the detection of H2O2 at concentrations as low as 1 pptv with an integration time of 10 seconds.

Dissipation dynamics of field-free molecular alignment for symmetric-top molecules: Ethane (C2H6)

NASA Astrophysics Data System (ADS)

Zhang, H.; Billard, F.; Yu, X.; Faucher, O.; Lavorel, B.

2018-03-01

The field-free molecular alignment of symmetric-top molecules, ethane, induced by intense non-resonant linearly polarized femtosecond laser pulses is investigated experimentally in the presence of collisional relaxation. The dissipation dynamics of field-free molecular alignment are measured by the balanced detection of ultrafast molecular birefringence of ethane gas samples at high pressures. By separating the molecular alignment into the permanent alignment and the transient alignment, the decay time-constants of both components are quantified at the same pressure. It is observed that the permanent alignment always decays slower compared to the transient alignment within the measured pressure range. This demonstrates that the propensity of molecules to conserve the orientation of angular momentum during collisions, previously observed for linear species, is also applicable to symmetric-top molecules. The results of this work provide valuable information for further theoretical understanding of collisional relaxation within nonlinear polyatomic molecules, which are expected to present interesting and nontrivial features due to an extra rotational degree of freedom.

Molecules of significance in planetary aeronomy

NASA Technical Reports Server (NTRS)

Mohan, H.

1979-01-01

This monograph is basically devoted to spectroscopic information of the molecules of planetary interest. Only those molecules have been dealt with which have been confirmed spectroscopically to be present in the atmosphere of major planets of our solar system and play an important role in the aeronomy of the respective planets. An introduction giving the general conditions of planets and their atmospheres including the gaseous molecules is given. Some typical planetary spectra is presented and supported with a discussion on some basic concepts of optical absorption and molecular parameters that are important to the study of planetary atmospheres. Quantities like dipole moments, transition probabilities, Einstein coefficients and line strengths, radiative life times, absorption cross sections, oscillator strengths, line widths and profiles, equivalent widths, growth curves, bond strengths, electronic transition moments, Franck-Condon factors and r-centroids, etc., are discussed. Spectroscopic information and relevant data of 6 diatomic (HF, HCL, CO, H2, O2, N2) and 6 polyatomic (CO2, N2), O3, HeO, NH3, CH4) molecules are presented.

Communication: XFAIMS—eXternal Field Ab Initio Multiple Spawning for electron-nuclear dynamics triggered by short laser pulses

DOE PAGES

Mignolet, Benoit; Curchod, Basile F. E.; Martinez, Todd J.

2016-11-17

Attoscience is an emerging field where attosecond pulses or few cycle IR pulses are used to pump and probe the correlated electron-nuclear motion of molecules. We present the trajectory-guided eXternal Field Ab Initio Multiple Spawning (XFAIMS) method that models such experiments “on-the-fly,” from laser pulse excitation to fragmentation or nonadiabatic relaxation to the ground electronic state. For the photoexcitation of the LiH molecule, we show that XFAIMS gives results in close agreement with numerically exact quantum dynamics simulations, both for atto- and femtosecond laser pulses. As a result, we then show the ability of XFAIMS to model the dynamics inmore » polyatomic molecules by studying the effect of nuclear motion on the photoexcitation of a sulfine (H 2CSO).« less

Scattering matrix approach to the dissociative recombination of HCO{sup +} and N{sub 2}H{sup +}

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fonseca dos Santos, S.; Douguet, N.; Orel, A. E.

We present a theoretical study of the indirect dissociative recombination of linear polyatomic ions at low collisional energies. The approach is based on the computation of the scattering matrix just above the ionization threshold and enables the explicit determination of all diabatic electronic couplings responsible for dissociative recombination. In addition, we use the multi-channel quantum-defect theory to demonstrate the precision of the scattering matrix by reproducing accurately ab initio Rydberg state energies of the neutral molecule. We consider the molecular ions N{sub 2}H{sup +} and HCO{sup +} as benchmark systems of astrophysical interest and improve former theoretical studies, which hadmore » repeatedly produced smaller cross sections than experimentally measured. Specifically, we demonstrate the crucial role of the previously overlooked stretching modes for linear polyatomic ions with large permanent dipole moment. The theoretical cross sections for both ions agree well with experimental data over a wide energy range. Finally, we consider the potential role of the HOC{sup +} isomer in the experimental cross sections of HCO{sup +} at energies below 10 meV.« less

Direct simulation Monte Carlo modeling of relaxation processes in polyatomic gases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pfeiffer, M., E-mail: mpfeiffer@irs.uni-stuttgart.de; Nizenkov, P., E-mail: nizenkov@irs.uni-stuttgart.de; Mirza, A., E-mail: mirza@irs.uni-stuttgart.de

2016-02-15

Relaxation processes of polyatomic molecules are modeled and implemented in an in-house Direct Simulation Monte Carlo code in order to enable the simulation of atmospheric entry maneuvers at Mars and Saturn’s Titan. The description of rotational and vibrational relaxation processes is derived from basic quantum-mechanics using a rigid rotator and a simple harmonic oscillator, respectively. Strategies regarding the vibrational relaxation process are investigated, where good agreement for the relaxation time according to the Landau-Teller expression is found for both methods, the established prohibiting double relaxation method and the new proposed multi-mode relaxation. Differences and applications areas of these two methodsmore » are discussed. Consequently, two numerical methods used for sampling of energy values from multi-dimensional distribution functions are compared. The proposed random-walk Metropolis algorithm enables the efficient treatment of multiple vibrational modes within a time step with reasonable computational effort. The implemented model is verified and validated by means of simple reservoir simulations and the comparison to experimental measurements of a hypersonic, carbon-dioxide flow around a flat-faced cylinder.« less

Direct simulation Monte Carlo modeling of relaxation processes in polyatomic gases

NASA Astrophysics Data System (ADS)

Pfeiffer, M.; Nizenkov, P.; Mirza, A.; Fasoulas, S.

2016-02-01

Relaxation processes of polyatomic molecules are modeled and implemented in an in-house Direct Simulation Monte Carlo code in order to enable the simulation of atmospheric entry maneuvers at Mars and Saturn's Titan. The description of rotational and vibrational relaxation processes is derived from basic quantum-mechanics using a rigid rotator and a simple harmonic oscillator, respectively. Strategies regarding the vibrational relaxation process are investigated, where good agreement for the relaxation time according to the Landau-Teller expression is found for both methods, the established prohibiting double relaxation method and the new proposed multi-mode relaxation. Differences and applications areas of these two methods are discussed. Consequently, two numerical methods used for sampling of energy values from multi-dimensional distribution functions are compared. The proposed random-walk Metropolis algorithm enables the efficient treatment of multiple vibrational modes within a time step with reasonable computational effort. The implemented model is verified and validated by means of simple reservoir simulations and the comparison to experimental measurements of a hypersonic, carbon-dioxide flow around a flat-faced cylinder.

Imaging a multidimensional multichannel potential energy surface: Photodetachment of H(-)(NH3) and NH4 (.).

PubMed

Hu, Qichi; Song, Hongwei; Johnson, Christopher J; Li, Jun; Guo, Hua; Continetti, Robert E

2016-06-28

Probes of the Born-Oppenheimer potential energy surfaces governing polyatomic molecules often rely on spectroscopy for the bound regions or collision experiments in the continuum. A combined spectroscopic and half-collision approach to image nuclear dynamics in a multidimensional and multichannel system is reported here. The Rydberg radical NH4 and the double Rydberg anion NH4 (-) represent a polyatomic system for benchmarking electronic structure and nine-dimensional quantum dynamics calculations. Photodetachment of the H(-)(NH3) ion-dipole complex and the NH4 (-) DRA probes different regions on the neutral NH4 PES. Photoelectron energy and angular distributions at photon energies of 1.17, 1.60, and 2.33 eV compare well with quantum dynamics. Photoelectron-photofragment coincidence experiments indicate dissociation of the nascent NH4 Rydberg radical occurs to H + NH3 with a peak kinetic energy of 0.13 eV, showing the ground state of NH4 to be unstable, decaying by tunneling-induced dissociation on a time scale beyond the present scope of multidimensional quantum dynamics.

Gaussian process model for extrapolation of scattering observables for complex molecules: From benzene to benzonitrile

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cui, Jie; Krems, Roman V.; Li, Zhiying

2015-10-21

We consider a problem of extrapolating the collision properties of a large polyatomic molecule A–H to make predictions of the dynamical properties for another molecule related to A–H by the substitution of the H atom with a small molecular group X, without explicitly computing the potential energy surface for A–X. We assume that the effect of the −H →−X substitution is embodied in a multidimensional function with unknown parameters characterizing the change of the potential energy surface. We propose to apply the Gaussian Process model to determine the dependence of the dynamical observables on the unknown parameters. This can bemore » used to produce an interval of the observable values which corresponds to physical variations of the potential parameters. We show that the Gaussian Process model combined with classical trajectory calculations can be used to obtain the dependence of the cross sections for collisions of C{sub 6}H{sub 5}CN with He on the unknown parameters describing the interaction of the He atom with the CN fragment of the molecule. The unknown parameters are then varied within physically reasonable ranges to produce a prediction uncertainty of the cross sections. The results are normalized to the cross sections for He — C{sub 6}H{sub 6} collisions obtained from quantum scattering calculations in order to provide a prediction interval of the thermally averaged cross sections for collisions of C{sub 6}H{sub 5}CN with He.« less

Multi-path variational transition state theory for chemical reaction rates of complex polyatomic species: ethanol + OH reactions.

PubMed

Zheng, Jingjing; Truhlar, Donald G

2012-01-01

Complex molecules often have many structures (conformations) of the reactants and the transition states, and these structures may be connected by coupled-mode torsions and pseudorotations; some but not all structures may have hydrogen bonds in the transition state or reagents. A quantitative theory of the reaction rates of complex molecules must take account of these structures, their coupled-mode nature, their qualitatively different character, and the possibility of merging reaction paths at high temperature. We have recently developed a coupled-mode theory called multi-structural variational transition state theory (MS-VTST) and an extension, called multi-path variational transition state theory (MP-VTST), that includes a treatment of the differences in the multi-dimensional tunneling paths and their contributions to the reaction rate. The MP-VTST method was presented for unimolecular reactions in the original paper and has now been extended to bimolecular reactions. The MS-VTST and MP-VTST formulations of variational transition state theory include multi-faceted configuration-space dividing surfaces to define the variational transition state. They occupy an intermediate position between single-conformation variational transition state theory (VTST), which has been used successfully for small molecules, and ensemble-averaged variational transition state theory (EA-VTST), which has been used successfully for enzyme kinetics. The theories are illustrated and compared here by application to three thermal rate constants for reactions of ethanol with hydroxyl radical--reactions with 4, 6, and 14 saddle points.

Spectral properties of minimal-basis-set orbitals: Implications for molecular electronic continuum states

NASA Astrophysics Data System (ADS)

Langhoff, P. W.; Winstead, C. L.

Early studies of the electronically excited states of molecules by John A. Pople and coworkers employing ab initio single-excitation configuration interaction (SECI) calculations helped to simulate related applications of these methods to the partial-channel photoionization cross sections of polyatomic molecules. The Gaussian representations of molecular orbitals adopted by Pople and coworkers can describe SECI continuum states when sufficiently large basis sets are employed. Minimal-basis virtual Fock orbitals stabilized in the continuous portions of such SECI spectra are generally associated with strong photoionization resonances. The spectral attributes of these resonance orbitals are illustrated here by revisiting previously reported experimental and theoretical studies of molecular formaldehyde (H2CO) in combination with recently calculated continuum orbital amplitudes.

Anharmonic Potential Constants and Their Dependence Upon Bond Length

DOE R&D Accomplishments Database

Herschbach, D. R.; Laurie, V. W.

1961-01-01

Empirical study of cubic and quartic vibrational force constants for diatomic molecules shows them to be approximately exponential functions of internuclear distance. A family of curves is obtained, determined by the location of the bonded atoms in rows of the periodic table. Displacements between successive curves correspond closely to those in Badger's rule for quadratic force constants (for which the parameters are redetermined to accord with all data now available). Constants for excited electronic and ionic states appear on practically the same curves as those for the ground states. Predictions based on the diatomic correlations agree with the available cubic constants for bond stretching in polyatomic molecules, regardless of the type of bonding involved. Implications of these regularities are discussed. (auth)

Direct Visualization of Valence Electron Motion Using Strong-Field Photoelectron Holography

NASA Astrophysics Data System (ADS)

He, Mingrui; Li, Yang; Zhou, Yueming; Li, Min; Cao, Wei; Lu, Peixiang

2018-03-01

Watching the valence electron move in molecules on its intrinsic timescale has been one of the central goals of attosecond science and it requires measurements with subatomic spatial and attosecond temporal resolutions. The time-resolved photoelectron holography in strong-field tunneling ionization holds the promise to access this realm. However, it remains to be a challenging task hitherto. Here we reveal how the information of valence electron motion is encoded in the hologram of the photoelectron momentum distribution (PEMD) and develop a novel approach of retrieval. As a demonstration, applying it to the PEMDs obtained by solving the time-dependent Schrödinger equation for the prototypical molecule H2+ , the attosecond charge migration is directly visualized with picometer spatial and attosecond temporal resolutions. Our method represents a general approach for monitoring attosecond charge migration in more complex polyatomic and biological molecules, which is one of the central tasks in the newly emerging attosecond chemistry.

Direct Visualization of Valence Electron Motion Using Strong-Field Photoelectron Holography.

PubMed

He, Mingrui; Li, Yang; Zhou, Yueming; Li, Min; Cao, Wei; Lu, Peixiang

2018-03-30

Watching the valence electron move in molecules on its intrinsic timescale has been one of the central goals of attosecond science and it requires measurements with subatomic spatial and attosecond temporal resolutions. The time-resolved photoelectron holography in strong-field tunneling ionization holds the promise to access this realm. However, it remains to be a challenging task hitherto. Here we reveal how the information of valence electron motion is encoded in the hologram of the photoelectron momentum distribution (PEMD) and develop a novel approach of retrieval. As a demonstration, applying it to the PEMDs obtained by solving the time-dependent Schrödinger equation for the prototypical molecule H_{2}^{+}, the attosecond charge migration is directly visualized with picometer spatial and attosecond temporal resolutions. Our method represents a general approach for monitoring attosecond charge migration in more complex polyatomic and biological molecules, which is one of the central tasks in the newly emerging attosecond chemistry.

Core-mass nonadiabatic corrections to molecules: H2, H2+, and isotopologues.

PubMed

Diniz, Leonardo G; Alijah, Alexander; Mohallem, José Rachid

2012-10-28

For high-precision calculations of rovibrational states of light molecules, it is essential to include non-adiabatic corrections. In the absence of crossings of potential energy surfaces, they can be incorporated in a single surface picture through coordinate-dependent vibrational and rotational reduced masses. We present a compact method for their evaluation and relate in particular the vibrational mass to a well defined nuclear core mass derived from a Mulliken analysis of the electronic density. For the rotational mass we propose a simple, but very effective parametrization. The use of these masses in the nuclear Schrödinger equation yields numerical data for the corrections of a much higher quality than can be obtained with optimized constant masses, typically better than 0.1 cm(-1). We demonstrate the method for H(2), H(2)(+), and singly deuterated isotopologues. Isotopic asymmetry does not present any particular difficulty. Generalization to polyatomic molecules is straightforward.

Simulated infrared emission spectra of highly excited polyatomic molecules: a detailed model of the PAH-UIR hypothesis

NASA Technical Reports Server (NTRS)

Cook, D. J.; Saykally, R. J.

1998-01-01

A detailed description of the polycyclic aromatic hydrocarbon (PAH)/unidentified infrared band (UIR) mechanism is presented in which experimental spectral bandshape functions are used to simulate IR emission spectra for individual molecules. These spectra are additively superimposed to produce a conglomerate spectrum representative of a family of PAH molecules. Ab initio vibrational frequencies and intensities for nine PAHs (neutral and cationic) as large as ovalene are used in conjunction with measured bandshape and temperature-dependent redshift data to simulate the UIR bands. The calculated spectra of cations provide a closer match to the UIRs than do those of the neutrals. However, the PAH cations used in the simulations fail to reproduce the details of the UIR emission spectra. The discrepancies are potentially alleviated if both larger PAHs and a greater number of PAHs were included in the simulation.

Theoretical investigation of gas-surface interactions

NASA Technical Reports Server (NTRS)

Dyall, Kenneth G.

1990-01-01

A Dirac-Hartree-Fock code was developed for polyatomic molecules. The program uses integrals over symmetry-adapted real spherical harmonic Gaussian basis functions generated by a modification of the MOLECULE integrals program. A single Gaussian function is used for the nuclear charge distribution, to ensure proper boundary conditions at the nuclei. The Gaussian primitive functions are chosen to satisfy the kinetic balance condition. However, contracted functions which do not necessarily satisfy this condition may be used. The Fock matrix is constructed in the scalar basis and transformed to a jj-coupled 2-spinor basis before diagonalization. The program was tested against numerical results for atoms with a Gaussian nucleus and diatomic molecules with point nuclei. The energies converge on the numerical values as the basis set size is increased. Full use of molecular symmetry (restricted to D sub 2h and subgroups) is yet to be implemented.

A new scale of electronegativity based on electrophilicity index.

PubMed

Noorizadeh, Siamak; Shakerzadeh, Ehsan

2008-04-17

By calculating the energies of neutral and different ionic forms (M2+, M+, M, M-, and M2-) of 32 elements (using B3LYP/6-311++G** level of theory) and taking energy (E) to be a Morse-like function of the number of electrons (N), the electrophilicity values (omega) are calculated for these atoms. The obtained electrophilicities show a good linearity with some commonly used electronegativity scales such as Pauling and Allred-Rochow. Using these electrophilicities, the ionicities of some diatomic molecules are calculated, which are in good agreement with the experimental data. Therefore, these electrophilicities are introduced as a new scale for atomic electronegativity, chi(omega)0. The same procedure is also performed for some simple polyatomic molecules. It is shown that the new scale successfully obeys Sanderson's electronegativity equalization principle and for those molecules which have the same number of atoms, the ratio of the change in electronegativity during the formation of a molecule from its elements to the molecular electronegativity (Delta chi/chi omega) is the same.

Stereocontrol of attosecond time-scale electron dynamics in ABCU using ultrafast laser pulses: a computational study.

PubMed

Mignolet, B; Gijsbertsen, A; Vrakking, M J J; Levine, R D; Remacle, F

2011-05-14

The attosecond time-scale electronic dynamics induced by an ultrashort laser pulse is computed using a multi configuration time dependent approach in ABCU (C(10)H(19)N), a medium size polyatomic molecule with a rigid cage geometry. The coupling between the electronic states induced by the strong pulse is included in the many electron Hamiltonian used to compute the electron dynamics. We show that it is possible to implement control of the electron density stereodynamics in this medium size molecule by varying the characteristics of the laser pulse, for example by polarizing the electric field either along the N-C axis of the cage, or in the plane perpendicular to it. The excitation produces an oscillatory, non-stationary, electronic state that exhibits localization of the electron density in different parts of the molecule both during and after the pulse. The coherent oscillations of the non-stationary electronic state are also demonstrated through the alternation of the dipole moment of the molecule.

Electron Interactions with Non-Linear Polyatomic Molecules and their Radicals and Ions

DTIC Science & Technology

1991-06-01

is the usual antisymmetrization operator to ensure Pauli principle. In the expansion (4.1.2), we have neglected the correlation functions of the (N...Kochem, K M Scheuerlein, K Jung and H Ehrhardt, J. Phys. B19, 3625 (1986). [27]. A Jain, Ph.D. thesis (Queen’s University, Belfast) 1983. [2S]. D M...Winstead and V McLoy, Phys. Rev. A42, 5357 (1990). [52]. R Muiller, K Jung , K H Kochem, W Sohn and H Ehrhardt, J. Phys. B 18, 3971 (1985). [53]. L

Calculating constants of the rates of the reactions of excitation, ionization, and atomic exchange: A model of a shock oscillator with a change of the Hamiltonian of the system

NASA Astrophysics Data System (ADS)

Tsyganov, D. L.

2017-11-01

A new model for calculating the rates of reactions of excitation, ionization, and atomic exchange is proposed. Diatomic molecule AB is an unstructured particle M upon the exchange of elastic-vibrational (VT) energy, i.e., a model of a shock forceful oscillator with a change in Hamiltonian (SFOH). The SFOH model is based on the quantum theory of strong perturbations. The SFOH model allows generalization in simulating the rates of the reactions of excitation, ionization, and atomic exchange in the vibrational-vibrational (VV) energy exchange of diatomic molecules, and the exchange of VV- and VT-energy of polyatomic molecules. The rate constants of the excitation of metastables A 3Σ u +, B 3Π g , W 3Δ u , B'3Σ u -, a'3Σ u -, and the ionization of a nitrogen molecules from ground state X2Σ g + upon a collision with a heavy structureless particle (a nitrogen molecule), are found as examples.

Towards a Quantum Dynamical Study of the H_2O+H_2O Inelastic Collision: Representation of the Potential and Preliminary Results

NASA Astrophysics Data System (ADS)

Ndengue, Steve Alexandre; Dawes, Richard

2017-06-01

Water, an essential ingredient of life, is prevalent in space and various media. H_2O in the gas phase is the major polyatomic species in the interstellar medium (ISM) and a primary target of current studies of collisional dynamics. In recent years a number of theoretical and experimental studies have been devoted to H_2O-X (with X=He, H_2, D_2, Ar, ?) elastic and inelastic collisions in an effort to understand rotational distributions of H_2O in molecular clouds. Although those studies treated several abundant species, no quantum mechanical calculation has been reported to date for a nonlinear polyatomic collider. We present in this talk the preliminary steps toward this goal, using the H_2O molecule itself as our collider, the very accurate MB-Pol surface to describe the intermolecular interaction and the MultiConfiguration Time Dependent (MCTDH) algorithm to study the dynamics. One main challenge in this effort is the need to express the Potential Energy Surface (PES) in a sum-of-products form optimal for MCTDH calculations. We will describe how this was done and present preliminary results of state-to-state probabilities.

Imaging a multidimensional multichannel potential energy surface: Photodetachment of H{sup −}(NH{sub 3}) and NH{sub 4}{sup −}

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hu, Qichi; Johnson, Christopher J.; Continetti, Robert E., E-mail: hguo@umn.edu, E-mail: rcontinetti@ucsd.edu

2016-06-28

Probes of the Born-Oppenheimer potential energy surfaces governing polyatomic molecules often rely on spectroscopy for the bound regions or collision experiments in the continuum. A combined spectroscopic and half-collision approach to image nuclear dynamics in a multidimensional and multichannel system is reported here. The Rydberg radical NH{sub 4} and the double Rydberg anion NH{sub 4}{sup −} represent a polyatomic system for benchmarking electronic structure and nine-dimensional quantum dynamics calculations. Photodetachment of the H{sup −}(NH{sub 3}) ion-dipole complex and the NH{sub 4}{sup −} DRA probes different regions on the neutral NH{sub 4} PES. Photoelectron energy and angular distributions at photon energiesmore » of 1.17, 1.60, and 2.33 eV compare well with quantum dynamics. Photoelectron-photofragment coincidence experiments indicate dissociation of the nascent NH{sub 4} Rydberg radical occurs to H + NH{sub 3} with a peak kinetic energy of 0.13 eV, showing the ground state of NH{sub 4} to be unstable, decaying by tunneling-induced dissociation on a time scale beyond the present scope of multidimensional quantum dynamics.« less

Data Needs for Stellar Atmosphere and Spectrum Modeling

NASA Technical Reports Server (NTRS)

Short, C. I.

2006-01-01

The main data need for stellar atmosphere and spectrum modeling remains atomic and molecular transition data, particularly energy levels and transition cross-sections. We emphasize that data is needed for bound-free (b - f) as well as bound-bound (b - b), and collisional as well as radiative transitions. Data is now needed for polyatomic molecules as well as atoms, ions, and diatomic molecules. In addition, data for the formation of, and extinction due to, liquid and solid phase dust grains is needed. A prioritization of species and data types is presented, and gives emphasis to Fe group elements, and elements important for the investigation of nucleosynthesis and Galactic chemical evolution, such as the -elements and n-capture elements. Special data needs for topical problems in the modeling of cool stars and brown dwarfs are described.

An advanced kinetic theory for morphing continuum with inner structures

NASA Astrophysics Data System (ADS)

Chen, James

2017-12-01

Advanced kinetic theory with the Boltzmann-Curtiss equation provides a promising tool for polyatomic gas flows, especially for fluid flows containing inner structures, such as turbulence, polyatomic gas flows and others. Although a Hamiltonian-based distribution function was proposed for diatomic gas flow, a general distribution function for the generalized Boltzmann-Curtiss equations and polyatomic gas flow is still out of reach. With assistance from Boltzmann's entropy principle, a generalized Boltzmann-Curtiss distribution for polyatomic gas flow is introduced. The corresponding governing equations at equilibrium state are derived and compared with Eringen's morphing (micropolar) continuum theory derived under the framework of rational continuum thermomechanics. Although rational continuum thermomechanics has the advantages of mathematical rigor and simplicity, the presented statistical kinetic theory approach provides a clear physical picture for what the governing equations represent.

Mixed Quantum/Classical Theory for Molecule-Molecule Inelastic Scattering: Derivations of Equations and Application to N2 + H2 System.

PubMed

Semenov, Alexander; Babikov, Dmitri

2015-12-17

The mixed quantum classical theory, MQCT, for inelastic scattering of two molecules is developed, in which the internal (rotational, vibrational) motion of both collision partners is treated with quantum mechanics, and the molecule-molecule scattering (translational motion) is described by classical trajectories. The resultant MQCT formalism includes a system of coupled differential equations for quantum probability amplitudes, and the classical equations of motion in the mean-field potential. Numerical tests of this theory are carried out for several most important rotational state-to-state transitions in the N2 + H2 system, in a broad range of collision energies. Besides scattering resonances (at low collision energies) excellent agreement with full-quantum results is obtained, including the excitation thresholds, the maxima of cross sections, and even some smaller features, such as slight oscillations of energy dependencies. Most importantly, at higher energies the results of MQCT are nearly identical to the full quantum results, which makes this approach a good alternative to the full-quantum calculations that become computationally expensive at higher collision energies and for heavier collision partners. Extensions of this theory to include vibrational transitions or general asymmetric-top rotor (polyatomic) molecules are relatively straightforward.

Constructing polyatomic potential energy surfaces by interpolating diabatic Hamiltonian matrices with demonstration on green fluorescent protein chromophore

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, Jae Woo; Rhee, Young Min, E-mail: ymrhee@postech.ac.kr; Department of Chemistry, Pohang University of Science and Technology

2014-04-28

Simulating molecular dynamics directly on quantum chemically obtained potential energy surfaces is generally time consuming. The cost becomes overwhelming especially when excited state dynamics is aimed with multiple electronic states. The interpolated potential has been suggested as a remedy for the cost issue in various simulation settings ranging from fast gas phase reactions of small molecules to relatively slow condensed phase dynamics with complex surrounding. Here, we present a scheme for interpolating multiple electronic surfaces of a relatively large molecule, with an intention of applying it to studying nonadiabatic behaviors. The scheme starts with adiabatic potential information and its diabaticmore » transformation, both of which can be readily obtained, in principle, with quantum chemical calculations. The adiabatic energies and their derivatives on each interpolation center are combined with the derivative coupling vectors to generate the corresponding diabatic Hamiltonian and its derivatives, and they are subsequently adopted in producing a globally defined diabatic Hamiltonian function. As a demonstration, we employ the scheme to build an interpolated Hamiltonian of a relatively large chromophore, para-hydroxybenzylidene imidazolinone, in reference to its all-atom analytical surface model. We show that the interpolation is indeed reliable enough to reproduce important features of the reference surface model, such as its adiabatic energies and derivative couplings. In addition, nonadiabatic surface hopping simulations with interpolation yield population transfer dynamics that is well in accord with the result generated with the reference analytic surface. With these, we conclude by suggesting that the interpolation of diabatic Hamiltonians will be applicable for studying nonadiabatic behaviors of sizeable molecules.« less

Intramolecular energy transfer and the driving mechanisms for large-amplitude collective motions of clusters

NASA Astrophysics Data System (ADS)

Yanao, Tomohiro; Koon, Wang Sang; Marsden, Jerrold E.

2009-04-01

This paper uncovers novel and specific dynamical mechanisms that initiate large-amplitude collective motions in polyatomic molecules. These mechanisms are understood in terms of intramolecular energy transfer between modes and driving forces. Structural transition dynamics of a six-atom cluster between a symmetric and an elongated isomer is highlighted as an illustrative example of what is a general message. First, we introduce a general method of hyperspherical mode analysis to analyze the energy transfer among internal modes of polyatomic molecules. In this method, the (3n-6) internal modes of an n-atom molecule are classified generally into three coarse level gyration-radius modes, three fine level twisting modes, and (3n-12) fine level shearing modes. We show that a large amount of kinetic energy flows into the gyration-radius modes when the cluster undergoes structural transitions by changing its mass distribution. Based on this fact, we construct a reactive mode as a linear combination of the three gyration-radius modes. It is shown that before the reactive mode acquires a large amount of kinetic energy, activation or inactivation of the twisting modes, depending on the geometry of the isomer, plays crucial roles for the onset of a structural transition. Specifically, in a symmetric isomer with a spherical mass distribution, activation of specific twisting modes drives the structural transition into an elongated isomer by inducing a strong internal centrifugal force, which has the effect of elongating the mass distribution of the system. On the other hand, in an elongated isomer, inactivation of specific twisting modes initiates the structural transition into a symmetric isomer with lower potential energy by suppressing the elongation effect of the internal centrifugal force and making the effects of the potential force dominant. This driving mechanism for reactions as well as the present method of hyperspherical mode analysis should be widely applicable to molecular reactions in which a system changes its overall mass distribution in a significant way.

The Spectroscopy and Photophysics of Aniline, 2-AMINOPYRIDINE, and 3-AMINOPYRIDINE

NASA Astrophysics Data System (ADS)

Kim, Byungjoo

1995-01-01

Two-photon ionization photoelectron spectroscopic techniques have been employed in concert with a picosecond laser system and molecular beam machine to study the vibrational structure of molecular ions and the intramolecular dynamics of optically prepared intermediate states. From photoelectron spectra of 2-aminopyridine via various S_1 vibronic resonances, the frequencies of several vibrations in the ionic state are assigned. The ionization potential of the molecule is found to be 8.099 +/- 0.003 eV. Using two-color ionization techniques, the electronic overlap effects in the photoionization of excited molecules have been studied, on the example of 2-aminopyridine, 3-aminopyridine, and aniline. The molecules are excited to their S_1 states, and ionized by a 200 nm laser pulse within 50 ps. The spectra of the aminopyridines show a striking absence of transitions to excited electronic states of the ions, indicating small electronic overlap factors in the ionization transitions and very little configuration interaction in the S _1 states. The spectra of aniline show the vibrationally resolved first excited electronic state band of the ion, which is very weak compared to the ground electronic state band, indicating a small amount of orbital mixing in the S_1 state. The vibrational peaks in the band were assigned by comparison of the spectra via two different vibronic resonances. The observations demonstrate that electronic overlap effects play a very general role in the ionization of polyatomic molecules in electronically excited states, and that orbital mixing patterns of the excited electronic states may become observable by projecting molecular electronic wavefunctions onto the ion states. In the time-delayed experiments for these molecules, all spectra reveal only one product of the nonradiative relaxation process. Careful considerations of electronic and vibrational overlap propensity rules for the ionization step lead to the conclusion that the dominant nonradiative decay mechanism in these molecules is the intersystem crossing to excited vibrational states of the T_1 state. This technique has been applied to study the predissociation process of CS_2 in the S_3 vibronic levels near 200 nm. The spectra show extensive vibrational structure, with unusual activity in the antisymmetric vibrations, indicating the possibility of level mixing in the intermediate state by the IVR couplings.

Constrained-pairing mean-field theory. IV. Inclusion of corresponding pair constraints and connection to unrestricted Hartree-Fock theory.

PubMed

Tsuchimochi, Takashi; Henderson, Thomas M; Scuseria, Gustavo E; Savin, Andreas

2010-10-07

Our previously developed constrained-pairing mean-field theory (CPMFT) is shown to map onto an unrestricted Hartree-Fock (UHF) type method if one imposes a corresponding pair constraint to the correlation problem that forces occupation numbers to occur in pairs adding to one. In this new version, CPMFT has all the advantages of standard independent particle models (orbitals and orbital energies, to mention a few), yet unlike UHF, it can dissociate polyatomic molecules to the correct ground-state restricted open-shell Hartree-Fock atoms or fragments.

Coupled-cluster treatment of molecular strong-field ionization

NASA Astrophysics Data System (ADS)

Jagau, Thomas-C.

2018-05-01

Ionization rates and Stark shifts of H2, CO, O2, H2O, and CH4 in static electric fields have been computed with coupled-cluster methods in a basis set of atom-centered Gaussian functions with a complex-scaled exponent. Consideration of electron correlation is found to be of great importance even for a qualitatively correct description of the dependence of ionization rates and Stark shifts on the strength and orientation of the external field. The analysis of the second moments of the molecular charge distribution suggests a simple criterion for distinguishing tunnel and barrier suppression ionization in polyatomic molecules.

Shock wave structure in rarefied polyatomic gases with large relaxation time for the dynamic pressure

NASA Astrophysics Data System (ADS)

Taniguchi, Shigeru; Arima, Takashi; Ruggeri, Tommaso; Sugiyama, Masaru

2018-05-01

The shock wave structure in rarefied polyatomic gases is analyzed based on extended thermodynamics (ET). In particular, the case with large relaxation time for the dynamic pressure, which corresponds to large bulk viscosity, is considered by adopting the simplest version of extended thermodynamics with only 6 independent fields (ET6); the mass density, the velocity, the temperature and the dynamic pressure. Recently, the validity of the theoretical predictions by ET was confirmed by the numerical analysis based on the kinetic theory in [S Kosuge and K Aoki: Phys. Rev. Fluids, Vol. 3, 023401 (2018)]. It was shown that numerical results using the polyatomic version of ellipsoidal statistical model agree with the theoretical predictions by ET for small or moderately large Mach numbers. In the present paper, first, we compare the theoretical predictions by ET6 with the ones by kinetic theory for large Mach number under the same assumptions, that is, the gas is polytropic and the bulk viscosity is proportional to the temperature. Second, the shock wave structure for large Mach number in a non-polytropic gas is analyzed with the particular interest in the effect of the temperature dependence of specific heat and the bulk viscosity on the shock wave structure. Through the analysis of the case of a rarefied carbon dioxide (CO2) gas, it is shown that these temperature dependences play important roles in the precise analysis of the structure for strong shock waves.

A table of polyatomic interferences in ICP-MS

USGS Publications Warehouse

May, Thomas W.; Wiedmeyer, Ray H.

1998-01-01

Spectroscopic interferences are probably the largest class of interferences in ICP-MS and are caused by atomic or molecular ions that have the same mass-to-charge as analytes of interest. Current ICP-MS instrumental software corrects for all known atomic “isobaric” interferences, or those caused by overlapping isotopes of different elements, but does not correct for most polyatomic interferences. Such interferences are caused by polyatomic ions that are formed from precursors having numerous sources, such as the sample matrix, reagents used for preparation, plasma gases, and entrained atmospheric gases.

Rotation driven translational diffusion of polyatomic ions in water: A novel mechanism for breakdown of Stokes-Einstein relation

NASA Astrophysics Data System (ADS)

Banerjee, Puja; Yashonath, Subramanian; Bagchi, Biman

2017-04-01

While most of the existing theoretical and simulation studies have focused on simple, spherical, halide and alkali ions, many chemically, biologically, and industrially relevant electrolytes involve complex non-spherical polyatomic ions like nitrate, chlorate, and sulfate to name only a few. Interestingly, some polyatomic ions in spite of being larger in size show anomalously high diffusivity and therefore cause a breakdown of the venerable Stokes-Einstein (S-E) relation between the size and diffusivity. Here we report a detailed analysis of the dynamics of anions in aqueous potassium nitrate (KNO3) and aqueous potassium acetate (CH3COOK) solutions. The two ions, nitrate (-NO3) and acetate (CH3-CO2 ), with their similar size show a large difference in diffusivity values. We present evidence that the translational motion of these polyatomic ions is coupled to the rotational motion of the ion. We show that unlike the acetate ion, nitrate ion with a symmetric charge distribution among all periphery oxygen atoms shows a faster rotational motion with large amplitude rotational jumps which enhances its translational motion due to translational-rotational coupling. By creating a family of modified-charge model systems, we have analysed the rotational motion of asymmetric polyatomic ions and the contribution of it to the translational motion. These model systems help clarifying and establishing the relative contribution of rotational motion in enhancing the diffusivity of the nitrate ion over the value predicted by the S-E relation and also over the other polyatomic ions having asymmetric charge distribution like the acetate ion. In the latter case, reduced rotational motion results in lower diffusivity values than those with symmetric charge distribution. We propose translational-rotational coupling as a general mechanism of the breakdown of the S-E relation in the case of polyatomic ions.

Rotation driven translational diffusion of polyatomic ions in water: A novel mechanism for breakdown of Stokes-Einstein relation.

PubMed

Banerjee, Puja; Yashonath, Subramanian; Bagchi, Biman

2017-04-28

While most of the existing theoretical and simulation studies have focused on simple, spherical, halide and alkali ions, many chemically, biologically, and industrially relevant electrolytes involve complex non-spherical polyatomic ions like nitrate, chlorate, and sulfate to name only a few. Interestingly, some polyatomic ions in spite of being larger in size show anomalously high diffusivity and therefore cause a breakdown of the venerable Stokes-Einstein (S-E) relation between the size and diffusivity. Here we report a detailed analysis of the dynamics of anions in aqueous potassium nitrate (KNO 3 ) and aqueous potassium acetate (CH 3 COOK) solutions. The two ions, nitrate (NO3-) and acetate (CH 3 CO2-), with their similar size show a large difference in diffusivity values. We present evidence that the translational motion of these polyatomic ions is coupled to the rotational motion of the ion. We show that unlike the acetate ion, nitrate ion with a symmetric charge distribution among all periphery oxygen atoms shows a faster rotational motion with large amplitude rotational jumps which enhances its translational motion due to translational-rotational coupling. By creating a family of modified-charge model systems, we have analysed the rotational motion of asymmetric polyatomic ions and the contribution of it to the translational motion. These model systems help clarifying and establishing the relative contribution of rotational motion in enhancing the diffusivity of the nitrate ion over the value predicted by the S-E relation and also over the other polyatomic ions having asymmetric charge distribution like the acetate ion. In the latter case, reduced rotational motion results in lower diffusivity values than those with symmetric charge distribution. We propose translational-rotational coupling as a general mechanism of the breakdown of the S-E relation in the case of polyatomic ions.

Theory of attosecond delays in molecular photoionization.

PubMed

Baykusheva, Denitsa; Wörner, Hans Jakob

2017-03-28

We present a theoretical formalism for the calculation of attosecond delays in molecular photoionization. It is shown how delays relevant to one-photon-ionization, also known as Eisenbud-Wigner-Smith delays, can be obtained from the complex dipole matrix elements provided by molecular quantum scattering theory. These results are used to derive formulae for the delays measured by two-photon attosecond interferometry based on an attosecond pulse train and a dressing femtosecond infrared pulse. These effective delays are first expressed in the molecular frame where maximal information about the molecular photoionization dynamics is available. The effects of averaging over the emission direction of the electron and the molecular orientation are introduced analytically. We illustrate this general formalism for the case of two polyatomic molecules. N 2 O serves as an example of a polar linear molecule characterized by complex photoionization dynamics resulting from the presence of molecular shape resonances. H 2 O illustrates the case of a non-linear molecule with comparably simple photoionization dynamics resulting from a flat continuum. Our theory establishes the foundation for interpreting measurements of the photoionization dynamics of all molecules by attosecond metrology.

Greenhouse effect in planetary atmospheres caused by molecular symmetry breaking in intermolecular interactions

NASA Astrophysics Data System (ADS)

Vigasin, A. A.; Mokhov, I. I.

2017-03-01

It is believed that the greenhouse effect is related to the parameters of absorption spectra of polyatomic molecules, usually trace gases, in planetary atmospheres. The main components of all known atmospheres of celestial bodies are symmetrical molecules that do not possess the dipole-allowed purely rotational (and in the case of diatomic molecules, vibrational-rotational) absorption spectrum. Upon increased pressure, a weak absorption appears, induced by intermolecular interaction, which can lead to a greenhouse effect. The contribution of the induced absorption in radiative forcing of a dense atmosphere may amount to a few or even tens of W/m2. In conditions typical for the atmospheres of terrestrial planets (including paleoatmospheres), the collision-induced absorption and associated greenhouse effect may lead to an increase in surface temperature above the freezing point of water. There is a correlation between the temperature of an atmosphere and the intermolecular bonding energy of gases that dominate in planetary atmospheres of the Solar System.

Correlation between molecular secondary ion yield and cluster ion sputtering for samples with different stopping powers

NASA Astrophysics Data System (ADS)

Heile, A.; Muhmann, C.; Lipinsky, D.; Arlinghaus, H. F.

2012-07-01

In static SIMS, the secondary ion yield, defined as detected ions per primary ion, can be increased by altering several primary ion parameters. For many years, no quantitative predictions could be made for the secondary ion yield enhancement of molecular ions. For thick samples of organic compounds, a power dependency of the secondary ion yield on the sputtering yield was shown. For this article, samples with thick molecular layers and (sub-)monolayers composed of various molecules were prepared on inorganic substrates such as silicon, silver, and gold, and subsequently analyzed. For primary ion bombardment, monoatomic (Ne+, Ar+, Ga+, Kr+, Xe+, Bi+) as well as polyatomic (Bin+, Bin++) primary ions were used within an energy range of 10-50 keV. The power dependency was found to hold true for the different samples; however, the exponent decreased with increasing stopping power. Based on these findings, a rule of thumb is proposed for the prediction of the lower limit of the secondary ion yield enhancement as a function of the primary ion species. Additionally, effects caused by the variation of the energy deposition are discussed, including the degree of molecular fragmentation and the non-linear increase of the secondary ion yield when polyatomic primary ions are used.

Strong-field ionization of linear molecules by a bicircular laser field: Symmetry considerations

NASA Astrophysics Data System (ADS)

Gazibegović-Busuladžić, A.; Busuladžić, M.; Hasović, E.; Becker, W.; Milošević, D. B.

2018-04-01

Using the improved molecular strong-field approximation, we investigate (high-order) above-threshold ionization [(H)ATI] of various linear polyatomic molecules by a two-color laser field of frequencies r ω and s ω (with integer numbers r and s ) having coplanar counter-rotating circularly polarized components (a so-called bicircular field). Reflection and rotational symmetries for molecules aligned in the laser-field polarization plane, analyzed for diatomic homonuclear molecules in Phys. Rev. A 95, 033411 (2017), 10.1103/PhysRevA.95.033411, are now considered for diatomic heteronuclear molecules and symmetric and asymmetric linear triatomic molecules. There are additional rotational symmetries for (H)ATI spectra of symmetric linear molecules compared to (H)ATI spectra of the asymmetric ones. It is shown that these symmetries manifest themselves differently for r +s odd and r +s even. For example, HATI spectra for symmetric molecules with r +s even obey inversion symmetry. For ATI spectra of linear molecules, reflection symmetry appears only for certain molecular orientation angles ±90∘-j r 180∘/(r +s ) (j integer). For symmetric linear molecules, reflection symmetry appears also for the angles -j r 180∘/(r +s ) . For perpendicular orientation of molecules with respect to the laser-field polarization plane, the HATI spectra are very similar to those of the atomic targets, i.e., both spectra are characterized by the same type of the (r +s )-fold symmetry.

Deuterium enrichment in the primitive ices of the protosolar nebula

NASA Technical Reports Server (NTRS)

Lutz, Barry L.; Owen, Tobias; De Bergh, Catherine

1990-01-01

On the basis of CH3D/CH4-ratio observations in the outer planets, the present effort to estimate the D/H ratio of the protosolar nebula's primitive ices arrives at two simple, yet effectively limiting models which constrain the degree of dilution undergone by deuterated volatiles through mixing with the initial hydrogen envelopes. These volatiles would have been contributed to planetary atmospheres by evaporated primordial ices. Ice D/H ratio model results of 0.0001 to 0.001 are compared with values for other potentially primitive material-containing bodies in the solar system, as well as with D/H ratio values from interstellar polyatomic molecules.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fujii, M.; Sato, K.; Kimura, K.

Photoelectron spectra due to autoionization for two series of high Rydberg states have been observed for diazabicyclooctane (DABCO) in a supersonic jet. The selection rule of the autoionization has been found to be ..delta..v = -1 for each vibrational mode involved in the Rydberg states, consistent with Berry's theory available for the vibrational autoionization of a polyatomic molecule. The relative autoionization efficiencies Phi/sub a/ for the high Rydberg series have also been determined from two-color MPI and fluorescence dip spectra. The irregular variation of Phi/sub a/ with the principal quantum number n has been found for the two Rydberg series,more » suggesting the irregular variation in their nonradiative rates« less

Prospects for P-bearing molecules in cometary atmospheres

NASA Astrophysics Data System (ADS)

Boice, Daniel; de Almeida, Amaury

Phosphorus is a key element in all known forms of life and phosphorus-bearing compounds have been observed in space. Phosphorus is ubiquitous in meteorites, albeit in small quantities, with phosphates being found in stoney meteorites and phosphides have been identified in iron meteorites. It has been detected as part of the dust component in comet Halley but searches for P-bearing species in the gas phase in comets have been unsuccessful. Based of its moderate cosmic abundance (eighteenth most abundant element, [P]/[N] = 4 x 10-3 ) and the positive identification of P-bearing species in the interstellar medium (such as, PN, PC, HCP and PO), we would expect simple molecules, diatomics (like PH, PO, PC, PS), triatomics (like HCP and PH2 ), and possibly other polyatomics (like phosphine PH3 and diphosphine P2 H4 ), to exist in cometary ices, hence released into the gas phase upon ice sublimation. Our fluid dynamics model with chemistry of cometary comae (SUISEI) has been adapted to study this problem. SUISEI produces cometocentric abundances of the coma gas species; velocities of the bulk gas, light atomic and molecular hydrogen with escape, and electrons; gas and electron temperatures; column densities to facilitate comparison with observations; coma energy budget quantities; attenuation of the solar irradiance; and other quantities that can be related readily to observations. We present results from the first quantitative study of phosphorus-bearing molecules in comets to identify likely species containing phosphorus to aid in future searches for this important element in comets, possibly shedding light on issues of comet formation (time and place) and matters of the prebiotic to biotic evolution of life. Acknowledgements. This work was supported by the NSF Planetary Astronomy Program.

Nonunique and nonuniform mapping in few-body Coulomb-explosion imaging

NASA Astrophysics Data System (ADS)

Sayler, A. M.; Eckner, E.; McKenna, J.; Esry, B. D.; Carnes, K. D.; Ben-Itzhak, I.; Paulus, G. G.

2018-03-01

Much of our knowledge of molecular geometry and interaction dynamics comes from indirect measurements of the molecular fragments following breakup. This technique—Coulomb-explosion imaging (CEI), i.e., determining the initial molecular configuration of a system from the momenta of the resulting fragments using knowledge of the particle interactions—is one of the fundamental tools of molecular physics. Moreover, CEI has been a staple of molecular studies for decades. Here we show that one often cannot assign a unique initial configuration to the few-body breakup of a polyatomic molecule given the measurement of the resulting fragments' momenta. Specifically, multiple initial configurations can result in identical momenta for a molecule breaking into three or more parts. Further, the nonunique and nonuniform mapping from the initial configuration to the measured momenta also significantly complicates the determination of molecular alignment at the time of breakup.

Imaging CF3I conical intersection and photodissociation dynamics by ultrafast electron diffraction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Jie

Conical intersections play a critical role in excited state dynamics of polyatomic molecules, as they govern the reaction pathways of many nonadiabatic processes. However, ultrafast probes have lacked sufficient spatial resolution to image wavepacket trajectories through these intersections directly. Here we present the simultaneous experimental characterization of one-photon and two-photon excitation channels in isolated CF3I molecules using ultrafast gas phase electron diffraction. In the two-photon channel, we have mapped out the real space trajectories of a coherent nuclear wavepacket, which bifurcates onto two potential energy surfaces when passing through a conical intersection. In the one-photon channel, we have resolved excitationmore » of both the umbrella and the breathing vibrational modes in the CF3 fragment in multiple nuclear dimensions. These findings benchmark and validate ab-initio nonadiabatic dynamics calculations.« less

Analysis of experimental heats of dilution of aqueous solutions of NaBPh 4 by use of the mean spherical approximation and molecular dynamics simulations

NASA Astrophysics Data System (ADS)

M'halla, Jalel; M'halla, Sondes; Wipff, Georges

2003-03-01

Calorimetric measurements of heats of dilution: QDC→0 =- nsφL,sexp, of aqueous solutions of NaBPh 4 are determined at 25 °C in the concentration range: 0

Interaction Between the Broad-Lined Type Ic Supernova 2012ap and Carriers of Diffuse Interstellar Bands

NASA Technical Reports Server (NTRS)

Milisavljevic, Dan; Margutti, Raffaella; Crabtree, Kyle N.; Foster, Jonathan B.; Soderberg, Alicia M.; Fesen, Robert A.; Parrent, Jerod T.; Sanders, Nathan E.; Drout, Maria R.; Kamble, Atish;

Time-resolved multi-mass ion imaging: Femtosecond UV-VUV pump-probe spectroscopy with the PImMS camera.

PubMed

Forbes, Ruaridh; Makhija, Varun; Veyrinas, Kévin; Stolow, Albert; Lee, Jason W L; Burt, Michael; Brouard, Mark; Vallance, Claire; Wilkinson, Iain; Lausten, Rune; Hockett, Paul

2017-07-07

The Pixel-Imaging Mass Spectrometry (PImMS) camera allows for 3D charged particle imaging measurements, in which the particle time-of-flight is recorded along with (x, y) position. Coupling the PImMS camera to an ultrafast pump-probe velocity-map imaging spectroscopy apparatus therefore provides a route to time-resolved multi-mass ion imaging, with both high count rates and large dynamic range, thus allowing for rapid measurements of complex photofragmentation dynamics. Furthermore, the use of vacuum ultraviolet wavelengths for the probe pulse allows for an enhanced observation window for the study of excited state molecular dynamics in small polyatomic molecules having relatively high ionization potentials. Herein, preliminary time-resolved multi-mass imaging results from C 2 F 3 I photolysis are presented. The experiments utilized femtosecond VUV and UV (160.8 nm and 267 nm) pump and probe laser pulses in order to demonstrate and explore this new time-resolved experimental ion imaging configuration. The data indicate the depth and power of this measurement modality, with a range of photofragments readily observed, and many indications of complex underlying wavepacket dynamics on the excited state(s) prepared.

Decelerating and Trapping Large Polar Molecules.

PubMed

Patterson, David

2016-11-18

Manipulating the motion of large polyatomic molecules, such as benzonitrile (C 6 H 5 CN), presents significant difficulties compared to the manipulation of diatomic molecules. Although recent impressive results have demonstrated manipulation, trapping, and cooling of molecules as large as CH 3 F, no general technique for trapping such molecules has been demonstrated, and cold neutral molecules larger than 5 atoms have not been trapped (M. Zeppenfeld, B. G. U. Englert, R. Glöckner, A. Prehn, M. Mielenz, C. Sommer, L. D. van Buuren, M. Motsch, G. Rempe, Nature 2012, 491, 570-573). In particular, extending Stark deceleration and electrostatic trapping to such species remains challenging. Here, we propose to combine a novel "asymmetric doublet state" Stark decelerator with recently demonstrated slow, cold, buffer-gas-cooled beams of closed-shell volatile molecules to realize a general system for decelerating and trapping samples of a broad range of volatile neutral polar prolate asymmetric top molecules. The technique is applicable to most stable volatile molecules in the 100-500 AMU range, and would be capable of producing trapped samples in a single rotational state and at a motional temperature of hundreds of mK. Such samples would immediately allow for spectroscopy of unprecedented resolution, and extensions would allow for further cooling and direct observation of slow intramolecular processes such as vibrational relaxation and Hertz-level tunneling dynamics. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Electron Scattering Studies of Gas Phase Molecular Structure at High Temperature

NASA Astrophysics Data System (ADS)

Mawhorter, Richard J., Jr.

A high precision counting electron diffraction study of the structure of gaseous sulfur dioxide as a function of temperature from 300(DEGREES) to 1000(DEGREES)K is presented. The results agree well with current theory, and yield insight into the effects of anharmonicity on molecular structure. Another aspect of molecular structure is the molecular charge density distribution. The difference (DELTA)(sigma) is between the electron scattering cross sections for the actual molecule and independent atom model (IAM) are a sensitive measure of the change in this distribution due to bond formation. These difference cross sections have been calculated using ab initio methods, and the results for a wide range of simple polyatomic molecules are presented. Such calculations are routinely done for a single, fixed molecular geometry, an approach which neglects the effects of the vibrational motion of real molecules. The effect of vibrational averaging is studied in detail for the three normal vibrational modes of H(,2)O in the ground state. The effects are small, lending credence to the practice of comparing cross sections calculated at a fixed geometry with inherently averaged experimental data. The efficacy of the standard formula used to account for vibrational averaging in the IAM is also examined. Finally, the nature of the ionic bond is probed with an experimental study of the structure of alkali chlorides, NaCl, KCl, RbCl, and CsCl, in the gas phase. Temperatures from 840-960(DEGREES)K were required to achieve the necessary vapor pressures of approximately 0.01 torr. A planar rhombic structure for the dimer molecule is confirmed, with a fairly uniform decrease of the chlorine-alkali-chlorine angle as the alkalis increase in size. The experiment also yields information on the amount of dimer present in the vapor, and these results are compared with thermodynamic values.

Atomic Rearrangements in Electron Attachment to Laser-Excited Molecules^*

NASA Astrophysics Data System (ADS)

Pinnaduwage, Lal; McCorkle, Dennis

1996-10-01

We report the observation of extensive atomic rearrangements in dissociative electron attachment to triethylamine " (Pinnaduwage and McCorkle, Chem.Phys. Lett. (in press, 1996))" and benzene laser excited to energies above their ionization thresholds. Large signal of "rearranged" negative ions, such as C_3^- (which is observed in both cases), were observed. This is in contrast to negative-ion formation via electron attachment to molecules in their ground states, where "rearranged" negative ions are comparatively weak and have been observed only occasionally. However, formation of "rearranged" positive ions is of common occurrence in the ionization of polyatomic molecules; it is possible that the formation of "rearranged" positive ions in the ionization processes, and the formation of such negative ions via electron attachment to excited states located close to the ionization threshold, are related. * Work supported by the LDRD Program of the Oak Ridge National Laboratory, managed by Lockheed Martin Energy Research Corp. for the US Department of Energy under contract number DE-AC05-96OR22464, and by the National Science Foundation under contract CHE-93113949 with the Univ. of Tenn., Knoxville.

Ultrafast Dynamics of 1,3-Cyclohexadiene in Highly Excited States

DOE PAGES

Bühler, Christine C.; Minitti, Michael P.; Deb, Sanghamitra; ...

2011-01-01

The ultrafast dynamics of 1,3-cyclohexadiene has been investigated via structurally sensitive Rydberg electron binding energies and shown to differ upon excitation to the 1B state and the 3p Rydberg state. Excitation of the molecule with 4.63 eV photons into the ultrashort-lived 1B state yields the well-known ring opening to 1,3,5-hexatriene, while a 5.99 eV photon lifts the molecule directly into the 3p-Rydberg state. Excitation to 3p does not induce ring opening. In both experiments, time-dependent shifts of the Rydberg electron binding energy reflect the structural dynamics of the molecular core. Structural distortions associated with 3p-excitation cause a dynamical shift in the -more » and -binding energies by 10 and 26 meV/ps, respectively, whereas after excitation into 1B, more severe structural transformations along the ring-opening coordinate produce shifts at a rate of 40 to 60 meV/ps. The experiment validates photoionization-photoelectron spectroscopy via Rydberg states as a powerful technique to observe structural dynamics of polyatomic molecules.« less

Separated-pair independent particle model and the generalized Brillouin theorem: ab initio calculations on the dissociation of polyatomic molecules

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sundberg, Kenneth Randall

1976-01-01

A method is developed to optimize the separated-pair independent particle (SPIP) wave function; it is a special case of the separated-pair theory obtained by using two-term natural expansions of the geminals. The orbitals are optimized by a theory based on the generalized Brillouin theorem and iterative configuration interaction (CI) calculations in the space of the SPIP function and its single excitations. The geminal expansion coefficients are optimized by serial 2 x 2 CI calculations. Formulas are derived for the matrix elements. An algorithm to implement the method is presented, and the work needed to evaluate the molecular integrals is discussed.

Computer program for calculating and fitting thermodynamic functions

NASA Technical Reports Server (NTRS)

Mcbride, Bonnie J.; Gordon, Sanford

1992-01-01

A computer program is described which (1) calculates thermodynamic functions (heat capacity, enthalpy, entropy, and free energy) for several optional forms of the partition function, (2) fits these functions to empirical equations by means of a least-squares fit, and (3) calculates, as a function of temperture, heats of formation and equilibrium constants. The program provides several methods for calculating ideal gas properties. For monatomic gases, three methods are given which differ in the technique used for truncating the partition function. For diatomic and polyatomic molecules, five methods are given which differ in the corrections to the rigid-rotator harmonic-oscillator approximation. A method for estimating thermodynamic functions for some species is also given.

Simulation of homogeneous condensation of small polyatomic systems in high pressure supersonic nozzle flows using Bhatnagar-Gross-Krook model

NASA Astrophysics Data System (ADS)

Kumar, Rakesh; Levin, Deborah A.

2011-03-01

In the present work, we have simulated the homogeneous condensation of carbon dioxide and ethanol using the Bhatnagar-Gross-Krook based approach. In an earlier work of Gallagher-Rogers et al. [J. Thermophys. Heat Transfer 22, 695 (2008)], it was found that it was not possible to simulate condensation experiments of Wegener et al. [Phys. Fluids 15, 1869 (1972)] using the direct simulation Monte Carlo method. Therefore, in this work, we have used the statistical Bhatnagar-Gross-Krook approach, which was found to be numerically more efficient than direct simulation Monte Carlo method in our previous studies [Kumar et al., AIAA J. 48, 1531 (2010)], to model homogeneous condensation of two small polyatomic systems, carbon dioxide and ethanol. A new weighting scheme is developed in the Bhatnagar-Gross-Krook framework to reduce the computational load associated with the study of homogeneous condensation flows. The solutions obtained by the use of the new scheme are compared with those obtained by the baseline Bhatnagar-Gross-Krook condensation model (without the species weighting scheme) for the condensing flow of carbon dioxide in the stagnation pressure range of 1-5 bars. Use of the new weighting scheme in the present work makes the simulation of homogeneous condensation of ethanol possible. We obtain good agreement between our simulated predictions for homogeneous condensation of ethanol and experiments in terms of the point of condensation onset and the distribution of mass fraction of ethanol condensed along the nozzle centerline.

Line Mixing in Parallel and Perpendicular Bands of CO2: A Further Test of the Refined Robert-Bonamy Formalism

NASA Technical Reports Server (NTRS)

Boulet, C.; Ma, Qiancheng; Tipping, R. H.

2015-01-01

Starting from the refined Robert-Bonamy formalism [Q. Ma, C. Boulet, and R. H. Tipping, J. Chem. Phys. 139, 034305 (2013)], we propose here an extension of line mixing studies to infrared absorptions of linear polyatomic molecules having stretching and bending modes. The present formalism does not neglect the internal degrees of freedom of the perturbing molecules, contrary to the energy corrected sudden (ECS) modeling, and enables one to calculate the whole relaxation matrix starting from the potential energy surface. Meanwhile, similar to the ECS modeling, the present formalism properly accounts for roles played by all the internal angular momenta in the coupling process, including the vibrational angular momentum. The formalism has been applied to the important case of CO2 broadened by N2. Applications to two kinds of vibrational bands (sigma yields sigma and sigma yields pi) have shown that the present results are in good agreement with both experimental data and results derived from the ECS model.

Comparison of different eigensolvers for calculating vibrational spectra using low-rank, sum-of-product basis functions

NASA Astrophysics Data System (ADS)

Leclerc, Arnaud; Thomas, Phillip S.; Carrington, Tucker

2017-08-01

Vibrational spectra and wavefunctions of polyatomic molecules can be calculated at low memory cost using low-rank sum-of-product (SOP) decompositions to represent basis functions generated using an iterative eigensolver. Using a SOP tensor format does not determine the iterative eigensolver. The choice of the interative eigensolver is limited by the need to restrict the rank of the SOP basis functions at every stage of the calculation. We have adapted, implemented and compared different reduced-rank algorithms based on standard iterative methods (block-Davidson algorithm, Chebyshev iteration) to calculate vibrational energy levels and wavefunctions of the 12-dimensional acetonitrile molecule. The effect of using low-rank SOP basis functions on the different methods is analysed and the numerical results are compared with those obtained with the reduced rank block power method. Relative merits of the different algorithms are presented, showing that the advantage of using a more sophisticated method, although mitigated by the use of reduced-rank SOP functions, is noticeable in terms of CPU time.

Role of electronic correlations in photoionization of NO2 in the vicinity of the 2A1/2B2 conical intersection.

PubMed

Brambila, Danilo S; Harvey, Alex G; Houfek, Karel; Mašín, Zdeněk; Smirnova, Olga

2017-08-02

We present the first ab initio multi-channel photoionization calculations for NO 2 in the vicinity of the 2 A 1 / 2 B 2 conical intersection, for a range of nuclear geometries, using our newly developed set of tools based on the ab initio multichannel R-matrix method. Electronic correlation is included in both the neutral and the scattering states of the molecule via configuration interaction. Configuration mixing is especially important around conical intersections and avoided crossings, both pertinent for NO 2 , and manifests itself via significant variations in photoelectron angular distributions. The method allows for a balanced and accurate description of the photoionization/photorecombination for a number of different ionic channels in a wide range of photoelectron energies up to 100 eV. Proper account of electron correlations is crucial for interpreting time-resolved signals in photoelectron spectroscopy and high harmonic generation (HHG) from polyatomic molecules.

Chemical Evolution of a Protoplanetary Disk

NASA Astrophysics Data System (ADS)

Semenov, Dmitry A.

2011-12-01

In this paper we review recent progress in our understanding of the chemical evolution of protoplanetary disks. Current observational constraints and theoretical modeling on the chemical composition of gas and dust in these systems are presented. Strong variations of temperature, density, high-energy radiation intensities in these disks, both radially and vertically, result in a peculiar disk chemical structure, where a variety of processes are active. In hot, dilute and heavily irradiated atmosphere only the most photostable simple radicals and atoms and atomic ions exist, formed by gas-phase processes. Beneath the atmosphere a partly UV-shielded, warm molecular layer is located, where high-energy radiation drives rich ion-molecule and radical-radical chemistry, both in the gas phase and on dust surfaces. In a cold, dense, dark disk midplane many molecules are frozen out, forming thick icy mantles where surface chemistry is active and where complex polyatomic (organic) species are synthesized. Dynamical processes affect disk chemical composition by enriching it in abundances of complex species produced via slow surface processes, which will become detectable with ALMA.

Nuclear relaxation and vibrational contributions to the static electrical properties of polyatomic molecules: beyond the Hartree-Fock approximation

NASA Astrophysics Data System (ADS)

Luis, Josep M.; Martí, Josep; Duran, Miquel; Andrés, JoséL.

1997-04-01

Electronic and nuclear contributions to the static molecular electrical properties, along with the Stark tuning rate ( δνE ) and the infrared cross section changes ( δSE) have been calculated at the SCF level and at different correlated levels of theory, using a TZ2P basis set and finite field techniques. Nuclear contributions to these molecular properties have also been calculated using a recent analytical approach that allow both to check the accuracy of the finite field values, and to evaluate the importance of higher-order derivatives. The HF, CO, H 2O, H 2CO, and CH 4 molecules have been studied and the results compared to experimental date when available. The paper shows that nuclear relaxation and vibrational contributions must be included in order to obtain accurate values of the static electrical properties. Two different, combined approaches are proposed to predict experimental values of the electrical properties to an error smaller than 5%.

Numerical-analytic implementation of the higher-order canonical Van Vleck perturbation theory for the interpretation of medium-sized molecule vibrational spectra.

PubMed

Krasnoshchekov, Sergey V; Isayeva, Elena V; Stepanov, Nikolay F

2012-04-12

Anharmonic vibrational states of semirigid polyatomic molecules are often studied using the second-order vibrational perturbation theory (VPT2). For efficient higher-order analysis, an approach based on the canonical Van Vleck perturbation theory (CVPT), the Watson Hamiltonian and operators of creation and annihilation of vibrational quanta is employed. This method allows analysis of the convergence of perturbation theory and solves a number of theoretical problems of VPT2, e.g., yields anharmonic constants y(ijk), z(ijkl), and allows the reliable evaluation of vibrational IR and Raman anharmonic intensities in the presence of resonances. Darling-Dennison and higher-order resonance coupling coefficients can be reliably evaluated as well. The method is illustrated on classic molecules: water and formaldehyde. A number of theoretical conclusions results, including the necessity of using sextic force field in the fourth order (CVPT4) and the nearly vanishing CVPT4 contributions for bending and wagging modes. The coefficients of perturbative Dunham-type Hamiltonians in high-orders of CVPT are found to conform to the rules of equality at different orders as earlier proven analytically for diatomic molecules. The method can serve as a good substitution of the more traditional VPT2.

Rigid rotators. [deriving the time-independent energy states associated with rotational motions of the molecule

NASA Technical Reports Server (NTRS)

1976-01-01

The two-particle, steady-state Schroedinger equation is transformed to center of mass and internuclear distance vector coordinates, leading to the free particle wave equation for the kinetic energy motion of the molecule and a decoupled wave equation for a single particle of reduced mass moving in a spherical potential field. The latter describes the vibrational and rotational energy modes of the diatomic molecule. For fixed internuclear distance, this becomes the equation of rigid rotator motion. The classical partition function for the rotator is derived and compared with the quantum expression. Molecular symmetry effects are developed from the generalized Pauli principle that the steady-state wave function of any system of fundamental particles must be antisymmetric. Nuclear spin and spin quantum functions are introduced and ortho- and para-states of rotators, along with their degeneracies, are defined. Effects of nuclear spin on entropy are deduced. Next, rigid polyatomic rotators are considered and the partition function for this case is derived. The patterns of rotational energy levels for nonlinear molecules are discussed for the spherical symmetric top, for the prolate symmetric top, for the oblate symmetric top, and for the asymmetric top. Finally, the equilibrium energy and specific heat of rigid rotators are derived.

Electron-molecule scattering in a strong laser field: Two-center interference effects

NASA Astrophysics Data System (ADS)

Dakić, J.; Habibović, D.; Čerkić, A.; Busuladžić, M.; Milošević, D. B.

2017-10-01

Laser-assisted scattering of electrons on diatomic molecules is considered using the S -matrix theory within the second Born approximation. The first term of the expansion in powers of the scattering potential corresponds to the direct or single laser-assisted scattering of electrons on molecular targets, while the second term of this expansion corresponds to the laser-assisted rescattering or double scattering. The rescattered electrons may have considerably higher energies in the final state than those that scattered only once. For multicenter polyatomic molecules scattering and rescattering may happen at any center and in any order. All these cases contribute to the scattering amplitude and the interference of different contributions leads to an increase or a decrease of the differential cross section in particular electron energy regions. For diatomic molecules there are two such contributions for single scattering and four contributions for double scattering. Analyzing the spectra of the scattered electrons, we find two interesting effects. For certain molecular orientations, the plateaus in the electron energy spectrum, characteristic of laser-assisted electron-atom scattering, are replaced by a sequence of gradually declining maxima, caused by the two-center interference effects. The second effect is the appearance of symmetric U -shaped structures in the angle-resolved energy spectra, which are described very well by the analytical formulas we provide.

Symbolic derivation of high-order Rayleigh-Schroedinger perturbation energies using computer algebra: Application to vibrational-rotational analysis of diatomic molecules

DOE Office of Scientific and Technical Information (OSTI.GOV)

Herbert, John M.

1997-01-01

Rayleigh-Schroedinger perturbation theory is an effective and popular tool for describing low-lying vibrational and rotational states of molecules. This method, in conjunction with ab initio techniques for computation of electronic potential energy surfaces, can be used to calculate first-principles molecular vibrational-rotational energies to successive orders of approximation. Because of mathematical complexities, however, such perturbation calculations are rarely extended beyond the second order of approximation, although recent work by Herbert has provided a formula for the nth-order energy correction. This report extends that work and furnishes the remaining theoretical details (including a general formula for the Rayleigh-Schroedinger expansion coefficients) necessary formore » calculation of energy corrections to arbitrary order. The commercial computer algebra software Mathematica is employed to perform the prohibitively tedious symbolic manipulations necessary for derivation of generalized energy formulae in terms of universal constants, molecular constants, and quantum numbers. As a pedagogical example, a Hamiltonian operator tailored specifically to diatomic molecules is derived, and the perturbation formulae obtained from this Hamiltonian are evaluated for a number of such molecules. This work provides a foundation for future analyses of polyatomic molecules, since it demonstrates that arbitrary-order perturbation theory can successfully be applied with the aid of commercially available computer algebra software.« less

Non-adiabatic dynamics close to conical intersections and the surface hopping perspective

PubMed Central

Malhado, João Pedro; Bearpark, Michael J.; Hynes, James T.

2014-01-01

Conical intersections play a major role in the current understanding of electronic de-excitation in polyatomic molecules, and thus in the description of photochemistry and photophysics of molecular systems. This article reviews aspects of the basic theory underlying the description of non-adiabatic transitions at conical intersections, with particular emphasis on the important case when the dynamics of the nuclei are treated classically. Within this classical nuclear motion framework, the main aspects of the surface hopping methodology in the conical intersection context are presented. The emerging picture from this treatment is that of electronic transitions around conical intersections dominated by the interplay of the nuclear velocity and the derivative non-adiabatic coupling vector field. PMID:25485263

Sensitivity of transitions in internal rotor molecules to a possible variation of the proton-to-electron mass ratio

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jansen, Paul; Ubachs, Wim; Bethlem, Hendrick L.

2011-12-15

Recently, methanol was identified as a sensitive target system to probe variations of the proton-to-electron mass ratio {mu}[Jansen et al., Phys. Rev. Lett. 106, 100801 (2011)]. The high sensitivity of methanol originates from the interplay between overall rotation and hindered internal rotation of the molecule; that is, transitions that convert internal rotation energy into overall rotation energy, or vice versa, have an enhanced sensitivity coefficient, K{sub {mu}}. As internal rotation is a common phenomenon in polyatomic molecules, it is likely that other molecules display similar or even larger effects. In this paper we generalize the concepts that form the foundationmore » of the high sensitivity in methanol and use this to construct an approximate model which makes it possible to estimate the sensitivities of transitions in internal rotor molecules with C{sub 3v} symmetry, without performing a full calculation of energy levels. We find that a reliable estimate of transition sensitivities can be obtained from the three rotational constants (A, B, and C) and three torsional constants (F, V{sub 3}, and {rho}). This model is verified by comparing obtained sensitivities for methanol, acetaldehyde, acetamide, methyl formate, and acetic acid with a full analysis of the molecular Hamiltonian. Of the molecules considered, methanol is by far the most suitable candidate for laboratory and cosmological tests searching for a possible variation of {mu}.« less

Rayleigh-Brillouin light scattering spectroscopy of nitrous oxide (N2O)

NASA Astrophysics Data System (ADS)

Wang, Y.; Liang, K.; van de Water, W.; Marques, W.; Ubachs, W.

2018-02-01

High signal-to-noise and high-resolution light scattering spectra are measured for nitrous oxide (N2O) gas at an incident wavelength of 403.00 nm, at 90° scattering, at room temperature and at gas pressures in the range 0.5 - 4 bar. The resulting Rayleigh-Brillouin light scattering spectra are compared to a number of models describing in an approximate manner the collisional dynamics and energy transfer in this gaseous medium of this polyatomic molecular species. The Tenti-S6 model, based on macroscopic gas transport coefficients, reproduces the scattering profiles in the entire pressure range at less than 2% deviation at a similar level as does the alternative kinetic Grad's 6-moment model, which is based on the internal collisional relaxation as a decisive parameter. A hydrodynamic model fails to reproduce experimental spectra for the low pressures of 0.5-1 bar, but yields very good agreement ( < 1%) in the pressure range 2 - 4 bar. While these three models have a different physical basis the internal molecular relaxation derived can for all three be described in terms of a bulk viscosity of ηb ∼(6 ± 2) ×10-5 Pa · s. A 'rough-sphere' model, previously shown to be effective to describe light scattering in SF6 gas, is not found to be suitable, likely in view of the non-sphericity and asymmetry of the N-N-O structured linear polyatomic molecule.

Investigation of the ellipsoidal-statistical Bhatnagar-Gross-Krook kinetic model applied to gas-phase transport of heat and tangential momentum between parallel walls

NASA Astrophysics Data System (ADS)

Gallis, M. A.; Torczynski, J. R.

2011-03-01

The ellipsoidal-statistical Bhatnagar-Gross-Krook (ES-BGK) kinetic model is investigated for steady gas-phase transport of heat, tangential momentum, and mass between parallel walls (i.e., Fourier, Couette, and Fickian flows). This investigation extends the original study of Cercignani and Tironi, who first applied the ES-BGK model to heat transport (i.e., Fourier flow) shortly after this model was proposed by Holway. The ES-BGK model is implemented in a molecular-gas-dynamics code so that results from this model can be compared directly to results from the full Boltzmann collision term, as computed by the same code with the direct simulation Monte Carlo (DSMC) algorithm of Bird. A gas of monatomic molecules is considered. These molecules collide in a pairwise fashion according to either the Maxwell or the hard-sphere interaction and reflect from the walls according to the Cercignani-Lampis-Lord model with unity accommodation coefficients. Simulations are performed at pressures from near-free-molecular to near-continuum. Unlike the BGK model, the ES-BGK model produces heat-flux and shear-stress values that both agree closely with the DSMC values at all pressures. However, for both interactions, the ES-BGK model produces molecular-velocity-distribution functions that are qualitatively similar to those determined for the Maxwell interaction from Chapman-Enskog theory for small wall temperature differences and moment-hierarchy theory for large wall temperature differences. Moreover, the ES-BGK model does not produce accurate values of the mass self-diffusion coefficient for either interaction. Nevertheless, given its reasonable accuracy for heat and tangential-momentum transport, its sound theoretical foundation (it obeys the H-theorem), and its available extension to polyatomic molecules, the ES-BGK model may be a useful method for simulating certain classes of single-species noncontinuum gas flows, as Cercignani suggested.

Detection of anions by normal Raman spectroscopy and surface-enhanced Raman spectroscopy of cationic-coated substrates.

PubMed

Mosier-Boss, P A; Lieberman, S H

2003-09-01

The use of normal Raman spectroscopy and surface-enhanced Raman spectroscopy (SERS) of cationic-coated silver and gold substrates to detect polyatomic anions in aqueous environments is examined. For normal Raman spectroscopy, using near-infrared excitation, linear concentration responses were observed. Detection limits varied from 84 ppm for perchlorate to 2600 ppm for phosphate. In general, detection limits in the ppb to ppm concentration range for the polyatomic anions were achieved using cationic-coated SERS substrates. Adsorption of the polyatomic anions on the cationic-coated SERS substrates was described by a Frumkin isotherm. The SERS technique could not be used to detect dichromate, as this anion reacted with the coatings to form thiol esters. A competitive complexation method was used to evaluate the interaction of chloride ion with the cationic coatings. Hydrogen bonding and pi-pi interactions play significant roles in the selectivity of the cationic coatings.

Shock-wave structure for a polyatomic gas with large bulk viscosity

NASA Astrophysics Data System (ADS)

Kosuge, Shingo; Aoki, Kazuo

2018-02-01

The structure of a standing plane shock wave in a polyatomic gas is investigated on the basis of kinetic theory, with special interest in gases with large bulk viscosities, such as CO2 gas. The ellipsoidal statistical model for a polyatomic gas is employed. First, the shock structure is computed numerically for various upstream Mach numbers and for various (large) values of the ratio of the bulk viscosity to the shear viscosity, and different types of profiles, such as the double-layer structure consisting of a thin upstream layer with a steep change and a much thicker downstream layer with a mild change, are obtained. Then, an asymptotic analysis for large values of the ratio is carried out, and an analytical solution that describes the different types of profiles obtained by the numerical analysis, such as the double-layer structure, correctly is obtained.

Determination of low concentrations of iron, arsenic, selenium, cadmium, and other trace elements in natural samples using an octopole collision/reaction cell equipped quadrupole-inductively coupled plasma mass spectrometer.

PubMed

Dial, Angela R; Misra, Sambuddha; Landing, William M

2015-04-30

Accurate determination of trace metals has many applications in environmental and life sciences, such as constraining the cycling of essential micronutrients in biological production and employing trace metals as tracers for anthropogenic pollution. Analysis of elements such as Fe, As, Se, and Cd is challenged by the formation of polyatomic mass spectrometric interferences, which are overcome in this study. We utilized an Octopole Collision/Reaction Cell (CRC)-equipped Quadrupole-Inductively Coupled Plasma Mass Spectrometer for the rapid analysis of small volume samples (~250 μL) in a variety of matrices containing HNO3 and/or HCl. Efficient elimination of polyatomic interferences was demonstrated by the use of the CRC in Reaction Mode (RM; H2 gas) and in Collision-Reaction Mode (CRM; H2 and He gas), in addition to hot plasma (RF power 1500 W) and cool plasma (600 W) conditions. It was found that cool plasma conditions with RM achieved the greatest signal sensitivity while maintaining low detection limits (i.e. (56) Fe in 0.44 M HNO3 has a sensitivity of 160,000 counts per second (cps)-per-1 µg L(-1) and a limit of detection (LoD) of 0.86 ng L(-1) ). The average external precision was ≤ ~10% for minor (≤10 µg L(-1) ) elements measured in a 1:100 dilution of NIST 1643e and for iron in rainwater samples under all instrumental operating conditions. An improved method has been demonstrated for the rapid multi-element analysis of trace metals that are challenged by polyatomic mass spectrometric interferences, with a focus on (56) Fe, (75) As, (78) Se and (111) Cd. This method can contribute to aqueous environmental geochemistry and chemical oceanography, as well as other fields such as forensic chemistry, agriculture, food chemistry, and pharmaceutical sciences. Copyright © 2015 John Wiley & Sons, Ltd.

Mass Spectrometry as a Preparative Tool for the Surface Science of Large Molecules

NASA Astrophysics Data System (ADS)

Rauschenbach, Stephan; Ternes, Markus; Harnau, Ludger; Kern, Klaus

2016-06-01

Measuring and understanding the complexity that arises when nanostructures interact with their environment are one of the major current challenges of nanoscale science and technology. High-resolution microscopy methods such as scanning probe microscopy have the capacity to investigate nanoscale systems with ultimate precision, for which, however, atomic scale precise preparation methods of surface science are a necessity. Preparative mass spectrometry (pMS), defined as the controlled deposition of m/z filtered ion beams, with soft ionization sources links the world of large, biological molecules and surface science, enabling atomic scale chemical control of molecular deposition in ultrahigh vacuum (UHV). Here we explore the application of high-resolution scanning probe microscopy and spectroscopy to the characterization of structure and properties of large molecules. We introduce the fundamental principles of the combined experiments electrospray ion beam deposition and scanning tunneling microscopy. Examples for the deposition and investigation of single particles, for layer and film growth, and for the investigation of electronic properties of individual nonvolatile molecules show that state-of-the-art pMS technology provides a platform analog to thermal evaporation in conventional molecular beam epitaxy. Additionally, it offers additional, unique features due to the use of charged polyatomic particles. This new field is an enormous sandbox for novel molecular materials research and demands the development of advanced molecular ion beam technology.

NASA Astrophysics Data System (ADS)

2017-11-01

To deal with these problems investigators usually rely on a calibration method that makes use of a substance with an accurately known set of interatomic distances. The procedure consists of carrying out a diffraction experiment on the chosen calibrating substance, determining the value of the distances with use of the nominal (meter) value of the voltage, and then correcting the nominal voltage by an amount that produces the distances in the calibration substance. Examples of gases that have been used for calibration are carbon dioxide, carbon tetrachloride, carbon disulfide, and benzene; solids such as zinc oxide smoke (powder) deposited on a screen or slit have also been used. The question implied by the use of any standard molecule is, how accurate are the interatomic distance values assigned to the standard? For example, a solid calibrant is subject to heating by the electron beam, possibly producing unknown changes in the lattice constants, and polyatomic gaseous molecules require corrections for vibrational averaging ("shrinkage") effects that are uncertain at best. It has lately been necessary for us to investigate this matter in connection with on-going studies of several molecules in which size is the most important issue. These studies indicated that our usual method for retrieval of data captured on film needed improvement. The following is an account of these two issues - the accuracy of the distances assigned to the chosen standard molecule, and the improvements in our methods of retrieving the scattered intensity data.

Chemiluminescence in cryogenic matrices

NASA Astrophysics Data System (ADS)

Lotnik, S. V.; Kazakov, Valeri P.

1989-04-01

The literature data on chemiluminescence (CL) in cryogenic matrices have been classified and correlated for the first time. The role of studies on phosphorescence and CL at low temperatures in the development of cryochemistry is shown. The features of low-temperature CL in matrices of nitrogen and inert gases (fine structure of spectra, matrix effects) and the data on the mobility and reactivity of atoms and radicals at very low temperatures are examined. The trends in the development of studies on CL in cryogenic matrices, such as the search for systems involving polyatomic molecules and extending the forms of CL reactions, are followed. The reactions of active nitrogen with hydrocarbons that are accompanied by light emission and CL in the oxidation of carbenes at T >= 77 K are examined. The bibliography includes 112 references.

Spectral difference Lanczos method for efficient time propagation in quantum control theory

NASA Astrophysics Data System (ADS)

Farnum, John D.; Mazziotti, David A.

2004-04-01

Spectral difference methods represent the real-space Hamiltonian of a quantum system as a banded matrix which possesses the accuracy of the discrete variable representation (DVR) and the efficiency of finite differences. When applied to time-dependent quantum mechanics, spectral differences enhance the efficiency of propagation methods for evolving the Schrödinger equation. We develop a spectral difference Lanczos method which is computationally more economical than the sinc-DVR Lanczos method, the split-operator technique, and even the fast-Fourier-Transform Lanczos method. Application of fast propagation is made to quantum control theory where chirped laser pulses are designed to dissociate both diatomic and polyatomic molecules. The specificity of the chirped laser fields is also tested as a possible method for molecular identification and discrimination.

High Pressure Noble Gas Alkali Vapor Mixtures and Their Visible and Infrared Excimer Bands.

DTIC Science & Technology

1980-02-01

Curry, and W. Bapper, "Visible emission bands of KXen polyatomic exciplexes ," Phys. Rev. Letters 41, 543 (1978). A. C. Tam, T. Yabuzaki, S. M. Curry...I178 Visible Emission Bands of KXe. Polyatomic Exciplexes ’. Yauviki.’ ) A. C. Tam, 0’ S. M. Curry, ( ) and W. liapper COdumble Ru’Iiati.op labor,, ,wy...giound electronic states. These temperature. " exciplex " molectle, are often gool laser species (2) The polyxetide band broadens substantially since the

Channel-resolved photo- and Auger-electron spectroscopy of halogenated hydrocarbons

NASA Astrophysics Data System (ADS)

Ablikim, Utuq; Kaderiya, B.; Kumarapan, V.; Kushawaha, R.; Rudenko, A.; Rolles, D.; Xiong, H.; Berrah, N.; Bomme, C.; Savelyev, E.; Kilcoyne, D.

2016-05-01

Inner-shell photoelectron and Auger electron spectra of polyatomic molecules such as halogenated hydrocarbons are typically hard to interpret and assign due to many overlapping states that form broad bands even in high-resolution measurements. With the help of electron-ion-ion coincidence measurements performed using the velocity map imaging technique, we are able to detect high-energy (<= 150 eV) photo- and Auger electrons in coincidence with two- or many-body ionic fragmentation channels. Such channel-resolved measurements allow disentangling the overlapping electronic structures and help assigning individual components of the electron spectra to specific potential surfaces and final states. In this work, we present measurements on CH3 I, CH2 IBr, and CH2 ICl molecules in the gas-phase using soft x-ray light provided by the Advanced Light Source at LBNL. This project is supported by the DOE, Office of Science, BES, Division of Chemical, Geological and Biological Sciences under Award Number DE-FG02-86ER13491 (U.A., B.K., V.K., A.R., D.R.) and Award Number DE-SC0012376 (H.X., N.B.).

Millimeter-wave Absorption Studies of Molecules in Diffuse Clouds

NASA Astrophysics Data System (ADS)

Lucas, Robert; Liszt, Harvey S.

1999-10-01

With IRAM instruments in the last few years, we have been using compact extragalactic millimeter wave radio sources as background objects to study the absorption spectrum of diffuse interstellar gas at millimeter wavelengths. The molecular content of interstellar gas has turned out to be unexpectedly rich. Simple polyatomic molecules such as HCO+, C2H are quite ubiquitous near the Galactic plane (beta < 15o), and many species are detected in some directions (CO, HCO+, H2CO, HCN, HNC, CN, C2H, C3H2, H2S, CS, HCS+, SO, SiO). Remarkable proportionality relations are found between related species such as HCO+ and OH, or CN, HCN and HNC. The high abundance of some species is still a challenge for current models of diffuse cloud chemistry. A factor of 10 increase in the sensitivity will make such studies achievable in denser clouds, where the chemistry is still more active and where abundances are nowadays only available by emission measurements, and thus subject to uncertainties due to sometimes poorly understood line formation and excitation conditions.

The role of axis embedding on rigid rotor decomposition analysis of variational rovibrational wave functions.

PubMed

Szidarovszky, Tamás; Fábri, Csaba; Császár, Attila G

2012-05-07

Approximate rotational characterization of variational rovibrational wave functions via the rigid rotor decomposition (RRD) protocol is developed for Hamiltonians based on arbitrary sets of internal coordinates and axis embeddings. An efficient and general procedure is given that allows employing the Eckart embedding with arbitrary polyatomic Hamiltonians through a fully numerical approach. RRD tables formed by projecting rotational-vibrational wave functions into products of rigid-rotor basis functions and previously determined vibrational eigenstates yield rigid-rotor labels for rovibrational eigenstates by selecting the largest overlap. Embedding-dependent RRD analyses are performed, up to high energies and rotational excitations, for the H(2) (16)O isotopologue of the water molecule. Irrespective of the embedding chosen, the RRD procedure proves effective in providing unambiguous rotational assignments at low energies and J values. Rotational labeling of rovibrational states of H(2) (16)O proves to be increasingly difficult beyond about 10,000 cm(-1), close to the barrier to linearity of the water molecule. For medium energies and excitations the Eckart embedding yields the largest RRD coefficients, thus providing the largest number of unambiguous rotational labels.

Rovibrational spectroscopy using a kinetic energy operator in Eckart frame and the multi-configuration time-dependent Hartree (MCTDH) approach

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sadri, Keyvan, E-mail: keyvan.sadri@pci.uni-heidelberg.de; Meyer, Hans-Dieter, E-mail: hans-dieter.meyer@pci.uni-heidelberg.de; Lauvergnat, David, E-mail: david.lauvergnat@u-psud.fr

2014-09-21

For computational rovibrational spectroscopy the choice of the frame is critical for an approximate separation of overall rotation from internal motions. To minimize the coupling between internal coordinates and rotation, Eckart proposed a condition [“Some studies concerning rotating axes and polyatomic molecules,” Phys. Rev. 47, 552–558 (1935)] and a frame that fulfills this condition is hence called an Eckart frame. A method is developed to introduce in a systematic way the Eckart frame for the expression of the kinetic energy operator (KEO) in the polyspherical approach. The computed energy levels of a water molecule are compared with those obtained usingmore » a KEO in the standard definition of the Body-fixed frame of the polyspherical approach. The KEO in the Eckart frame leads to a faster convergence especially for large J states and vibrationally excited states. To provide an example with more degrees of freedom, rotational states of the vibrational ground state of the trans nitrous acid (HONO) are also investigated.« less

Final Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

McLuckey, Scott

2016-08-30

The overall objectives of this research effort were to expand the capabilities of spectroscopic and ion chemistry tools for the structural characterization of polyatomic ions of relevance to the broad mission of the Department of Energy. Mass spectrometry currently plays an important role in virtually all of the molecular sciences by virtue of the value of the accurate measurement of mass and the structural information that can be derived from various structural probes based on, for example, ion chemistry, ion mobility, and ion spectroscopy. Mass spectrometry has long played important roles in supporting the missions of the Department of Energymore » and its predecessor agencies, particularly in the area of isotopic analysis of nuclides. Molecular mass spectrometry has played increasingly important roles is many aspects of the production and use of energy as the nation has diversified its energy portfolio. There is an ongoing need for the expansion of the measurement capabilities associated with molecular mass spectrometry that involves both technological developments as well as improved understanding of the chemical and physical processes that take place upon ionization and ion analysis in a mass spectrometer. Advances in mass spectrometry have impacted science broadly and further advances will be required to meet the needs of current energy and environmental research. This program has historically focused on the structural characterization of polyatomic ions, usually within the context of a tandem mass spectrometry experiment. A wide variety of physical and chemical processes can take place within a mass spectrometer and advantage can be taken of such processes to enhance the quality and quantity of information that can be derived for a given chemical system of interest. For example, ions can undergo interactions with neutral molecules/atoms, light, surfaces, electrons, or oppositely charged ions. The outcomes of all such interactions can be sensitive to the structures of the ions and are therefore candidates for probes of ion structure. This program has historically focused on the chemistry and physics associated with ion/neutral interactions at both low and high translational energies, and ion/ion reactions. The former area has involved the study of ion/molecule reactions at thermal energies and the extensive study of collisional activation under a wide variety of conditions. A major area of emphasis has been collisional activation in electrodynamic ion traps. The study of gas-phase ion/ion reactions within the context of tandem mass spectrometry was initiated in this program and has grown to be a major research area in this group. Most of the focus in ion/ion chemistry has been on proton transfer and electron transfer reactions and some of the work in the previous budget period was directed, in particular, to fundamental aspects of electron transfer. Recently, the discovery of selective covalent ion/ion reactions has opened up new vistas for research that will expand significantly the capabilities of tandem mass spectrometry for the structural characterization of polyatomic ions.« less

Reference interaction site model with hydrophobicity induced density inhomogeneity: An analytical theory to compute solvation properties of large hydrophobic solutes in the mixture of polyatomic solvent molecules.

PubMed

Cao, Siqin; Sheong, Fu Kit; Huang, Xuhui

2015-08-07

Reference interaction site model (RISM) has recently become a popular approach in the study of thermodynamical and structural properties of the solvent around macromolecules. On the other hand, it was widely suggested that there exists water density depletion around large hydrophobic solutes (>1 nm), and this may pose a great challenge to the RISM theory. In this paper, we develop a new analytical theory, the Reference Interaction Site Model with Hydrophobicity induced density Inhomogeneity (RISM-HI), to compute solvent radial distribution function (RDF) around large hydrophobic solute in water as well as its mixture with other polyatomic organic solvents. To achieve this, we have explicitly considered the density inhomogeneity at the solute-solvent interface using the framework of the Yvon-Born-Green hierarchy, and the RISM theory is used to obtain the solute-solvent pair correlation. In order to efficiently solve the relevant equations while maintaining reasonable accuracy, we have also developed a new closure called the D2 closure. With this new theory, the solvent RDFs around a large hydrophobic particle in water and different water-acetonitrile mixtures could be computed, which agree well with the results of the molecular dynamics simulations. Furthermore, we show that our RISM-HI theory can also efficiently compute the solvation free energy of solute with a wide range of hydrophobicity in various water-acetonitrile solvent mixtures with a reasonable accuracy. We anticipate that our theory could be widely applied to compute the thermodynamic and structural properties for the solvation of hydrophobic solute.

Surface patterning of GaAs under irradiation with very heavy polyatomic Au ions

NASA Astrophysics Data System (ADS)

Bischoff, L.; Böttger, R.; Heinig, K.-H.; Facsko, S.; Pilz, W.

2014-08-01

Self-organization of surface patterns on GaAs under irradiation with heavy polyatomic Au ions has been observed. The patterns depend on the ion mass, and the substrate temperature as well as the incidence angle of the ions. At room temperature, under normal incidence the surface remains flat, whereas above 200 °C nanodroplets of Ga appear after irradiation with monatomic, biatomic as well as triatomic Au ions of kinetic energies in the range of 10-30 keV per atom. In the intermediate temperature range of 100-200 °C meander- and dot-like patterns form, which are not related to Ga excess. Under oblique ion incidence up to 45° from the surface normal, at room temperature the surface remains flat for mon- and polyatomic Au ions. For bi- and triatomic ions in the range of 60° ≤ α ≤ 70° ripple patterns have been found, which become shingle-like for α ≥ 80°, whereas the surface remains flat for monatomic ions.

Dynamics of photoionization from molecular electronic wavepacket states in intense pulse laser fields: A nonadiabatic electron wavepacket study.

PubMed

Matsuoka, Takahide; Takatsuka, Kazuo

2017-04-07

A theory for dynamics of molecular photoionization from nonadiabatic electron wavepackets driven by intense pulse lasers is proposed. Time evolution of photoelectron distribution is evaluated in terms of out-going electron flux (current of the probability density of electrons) that has kinetic energy high enough to recede from the molecular system. The relevant electron flux is in turn evaluated with the complex-valued electronic wavefunctions that are time evolved in nonadiabatic electron wavepacket dynamics in laser fields. To uniquely rebuild such wavefunctions with its electronic population being lost by ionization, we adopt the complex-valued natural orbitals emerging from the electron density as building blocks of the total wavefunction. The method has been implemented into a quantum chemistry code, which is based on configuration state mixing for polyatomic molecules. Some of the practical aspects needed for its application will be presented. As a first illustrative example, we show the results of hydrogen molecule and its isotope substitutes (HD and DD), which are photoionized by a two-cycle pulse laser. Photon emission spectrum associated with above threshold ionization is also shown. Another example is taken from photoionization dynamics from an excited state of a water molecule. Qualitatively significant effects of nonadiabatic interaction on the photoelectron spectrum are demonstrated.

RichMol: A general variational approach for rovibrational molecular dynamics in external electric fields

NASA Astrophysics Data System (ADS)

Owens, Alec; Yachmenev, Andrey

2018-03-01

In this paper, a general variational approach for computing the rovibrational dynamics of polyatomic molecules in the presence of external electric fields is presented. Highly accurate, full-dimensional variational calculations provide a basis of field-free rovibrational states for evaluating the rovibrational matrix elements of high-rank Cartesian tensor operators and for solving the time-dependent Schrödinger equation. The effect of the external electric field is treated as a multipole moment expansion truncated at the second hyperpolarizability interaction term. Our fully numerical and computationally efficient method has been implemented in a new program, RichMol, which can simulate the effects of multiple external fields of arbitrary strength, polarization, pulse shape, and duration. Illustrative calculations of two-color orientation and rotational excitation with an optical centrifuge of NH3 are discussed.

The creation of hypersonic flows by a powerful impulse capillary discharge

NASA Astrophysics Data System (ADS)

Pashchina, A. S.; Karmatsky, R. E.; Klimov, A. I.

2017-11-01

The possibility of using a powerful pulsed capillary discharge to produce quasi-stationary highspeed plasma flows with characteristic Mach numbers M = 3-10 and temperatures T = 3000-6000 K has been experimentally substantiated. In a rarefied gas atmosphere ( p ∞ < 10 Torr), the transverse size of flow exceeds d < 3 cm and the duration of the working cycle can be brought to hundreds of milliseconds, which is of interest in problems of laboratory modeling of physical-chemical and gas-dynamic effects of interaction of bodies with hypersonic flows. Strong temperature nonequilibrium has been found (with the ratio between the vibrational and rotational temperatures reaching T v/ T r = 3 and more) and anomalously low values of the effective adiabatic index, which indicates an intensive formation of polyatomic molecules and condensed particles in a carbon-containing plasma.

Creation of Rydberg Polarons in a Bose Gas

NASA Astrophysics Data System (ADS)

Camargo, F.; Schmidt, R.; Whalen, J. D.; Ding, R.; Woehl, G.; Yoshida, S.; Burgdörfer, J.; Dunning, F. B.; Sadeghpour, H. R.; Demler, E.; Killian, T. C.

2018-02-01

We report spectroscopic observation of Rydberg polarons in an atomic Bose gas. Polarons are created by excitation of Rydberg atoms as impurities in a strontium Bose-Einstein condensate. They are distinguished from previously studied polarons by macroscopic occupation of bound molecular states that arise from scattering of the weakly bound Rydberg electron from ground-state atoms. The absence of a p -wave resonance in the low-energy electron-atom scattering in Sr introduces a universal behavior in the Rydberg spectral line shape and in scaling of the spectral width (narrowing) with the Rydberg principal quantum number, n . Spectral features are described with a functional determinant approach (FDA) that solves an extended Fröhlich Hamiltonian for a mobile impurity in a Bose gas. Excited states of polyatomic Rydberg molecules (trimers, tetrameters, and pentamers) are experimentally resolved and accurately reproduced with a FDA.

Coherent electron emission beyond Young-type interference from diatomic molecules

NASA Astrophysics Data System (ADS)

Agueny, H.; Makhoute, A.; Dubois, A.; Hansen, J. P.

2016-01-01

It has been known for more than 15 years that the differential cross section of electrons emitted from diatomic molecules during interaction with energetic charged particles oscillates as a function of electron momentum. The origin of the phenomenon is two-center interference, which naturally relates it back to the Young double-slit experiment. In addition to a characteristic frequency which can be described by lowest-order perturbation theories, the observation and origin of higher-order harmonics of the basic oscillation frequency has been much discussed. Here, we show that high harmonics of the fundamental Young-type oscillation frequency observed in electron spectra in fast ion-molecule collisions can be clearly exposed in numerical solutions of the time-dependent Schrödinger equation within a one-dimensional model. Momentum distribution of the ejected electron is analyzed and shows that the phenomenon emerges when the charged particle beam collides with diatomic molecules with substantial large internuclear distance. Frequency spectra from nonperturbative calculations for electron emission from Rb2+ and Cs2+ exhibit a pronounced high-order oscillation in contrast to similar close-coupling calculations performed on H2 targets. The electron emission from these heavy molecules contains second- and third-order harmonics which are fully reproduced in an analytic model based on the Born series. Extending to triatomic molecular targets displays an increased range of harmonics. This suggests that electron emission spectra from new experiments on heavy diatomic and linear polyatomic molecular targets may provide a unique insight into competing coherent emission mechanisms and their relative strength.

Entropy, energy, and entanglement of localized states in bent triatomic molecules

NASA Astrophysics Data System (ADS)

Yuan, Qiang; Hou, Xi-Wen

2017-05-01

The dynamics of quantum entropy, energy, and entanglement is studied for various initial states in an important spectroscopic Hamiltonian of bent triatomic molecules H2O, D2O, and H2S. The total quantum correlation is quantified in terms of the mutual information and the entanglement by the concurrence borrowed from the theory of quantum information. The Pauli entropy and the intramolecular energy usually used in the theory of molecules are calculated to establish a possible relationship between both theories. Sections of two quantities among these four quantities are introduced to visualize such relationship. Analytic and numerical simulations demonstrate that if an initial state is taken to be the stretch- or the bend-vibrationally localized state, the mutual information, the Pauli entropy, and the concurrence are dominant-positively correlated while they are dominantly anti-correlated with the interacting energy among three anharmonic vibrational modes. In particular, such correlation is more distinct for the localized state with high excitations in the bending mode. The nice quasi-periodicity of those quantities in D2O molecule reveals that this molecule prepared in the localized state in the stretching or the bending mode can be more appreciated for molecular quantum computation. However, the dynamical correlations of those quantities behave irregularly for the dislocalized states. Moreover, the hierarchy of the mutual information and the Pauli entropy is explicitly proved. Quantum entropy and energy in every vibrational mode are investigated. Thereby, the relation between bipartite and tripartite entanglements is discussed as well. Those are useful for the understanding of quantum correlations in high-dimensional states in polyatomic molecules from quantum information and intramolecular dynamics.

Can Internal Conversion BE Controlled by Mode-Specific Vibrational Excitation in Polyatomic Molecules

NASA Astrophysics Data System (ADS)

Portnov, Alexander; Epshtein, Michael; Bar, Ilana

2017-06-01

Nonadiabatic processes, dominated by dynamic passage of reactive fluxes through conical intersections (CIs) are considered to be appealing means for manipulating reaction paths. One approach that is considered to be effective in controlling the course of dissociation processes is the selective excitation of vibrational modes containing a considerable component of motion. Here, we have chosen to study the predissociation of the model test molecule, methylamine and its deuterated isotopologues, excited to well-characterized quantum states on the first excited electronic state, S_{1}, by following the N-H(D) bond fission dynamics through sensitive H(D) photofragment probing. The branching ratios between slow and fast H(D) photofragments, the internal energies of their counter radical photofragments and the anisotropy parameters for fast H photofragments, confirm correlated anomalies for predissociation initiated from specific rovibronic states, reflecting the existence of a dynamic resonance in each molecule. This resonance strongly depends on the energy of the initially excited rovibronic states, the evolving vibrational mode on the repulsive S_{1} part during N-H(D) bond elongation, and the manipulated passage through the CI that leads to radicals excited with C-N-H(D) bending and preferential perpendicular bond breaking, relative to the photolyzing laser polarization, in molecules containing the NH_{2} group. The indicated resonance plays an important role in the bifurcation dynamics at the CI and can be foreseen to exist in other photoinitiated processes and to control their outcome.

Structure factors for tunneling ionization rates of molecules: General Hartree-Fock-based integral representation

NASA Astrophysics Data System (ADS)

Madsen, Lars Bojer; Jensen, Frank; Dnestryan, Andrey I.; Tolstikhin, Oleg I.

2017-07-01

In the leading-order approximation of the weak-field asymptotic theory (WFAT), the dependence of the tunneling ionization rate of a molecule in an electric field on its orientation with respect to the field is determined by the structure factor of the ionizing molecular orbital. The WFAT yields an expression for the structure factor in terms of a local property of the orbital in the asymptotic region. However, in general quantum chemistry approaches molecular orbitals are expanded in a Gaussian basis which does not reproduce their asymptotic behavior correctly. This hinders the application of the WFAT to polyatomic molecules, which are attracting increasing interest in strong-field physics. Recently, an integral-equation approach to the WFAT for tunneling ionization of one electron from an arbitrary potential has been developed. The structure factor is expressed in an integral form as a matrix element involving the ionizing orbital. The integral is not sensitive to the asymptotic behavior of the orbital, which resolves the difficulty mentioned above. Here, we extend the integral representation for the structure factor to many-electron systems treated within the Hartree-Fock method and show how it can be implemented on the basis of standard quantum chemistry software packages. We validate the methodology by considering noble-gas atoms and the CO molecule, for which accurate structure factors exist in the literature. We also present benchmark results for CO2 and for NH3 in the pyramidal and planar geometries.

Preparation and coherent manipulation of pure quantum states of a single molecular ion

NASA Astrophysics Data System (ADS)

Chou, Chin-Wen; Kurz, Christoph; Hume, David B.; Plessow, Philipp N.; Leibrandt, David R.; Leibfried, Dietrich

2017-05-01

Laser cooling and trapping of atoms and atomic ions has led to advances including the observation of exotic phases of matter, the development of precision sensors and state-of-the-art atomic clocks. The same level of control in molecules could also lead to important developments such as controlled chemical reactions and sensitive probes of fundamental theories, but the vibrational and rotational degrees of freedom in molecules pose a challenge for controlling their quantum mechanical states. Here we use quantum-logic spectroscopy, which maps quantum information between two ion species, to prepare and non-destructively detect quantum mechanical states in molecular ions. We develop a general technique for optical pumping and preparation of the molecule into a pure initial state. This enables us to observe high-resolution spectra in a single ion (CaH+) and coherent phenomena such as Rabi flopping and Ramsey fringes. The protocol requires a single, far-off-resonant laser that is not specific to the molecule, so many other molecular ions, including polyatomic species, could be treated using the same methods in the same apparatus by changing the molecular source. Combined with the long interrogation times afforded by ion traps, a broad range of molecular ions could be studied with unprecedented control and precision. Our technique thus represents a critical step towards applications such as precision molecular spectroscopy, stringent tests of fundamental physics, quantum computing and precision control of molecular dynamics.

Preparation and coherent manipulation of pure quantum states of a single molecular ion.

PubMed

Chou, Chin-Wen; Kurz, Christoph; Hume, David B; Plessow, Philipp N; Leibrandt, David R; Leibfried, Dietrich

2017-05-10

Laser cooling and trapping of atoms and atomic ions has led to advances including the observation of exotic phases of matter, the development of precision sensors and state-of-the-art atomic clocks. The same level of control in molecules could also lead to important developments such as controlled chemical reactions and sensitive probes of fundamental theories, but the vibrational and rotational degrees of freedom in molecules pose a challenge for controlling their quantum mechanical states. Here we use quantum-logic spectroscopy, which maps quantum information between two ion species, to prepare and non-destructively detect quantum mechanical states in molecular ions. We develop a general technique for optical pumping and preparation of the molecule into a pure initial state. This enables us to observe high-resolution spectra in a single ion (CaH + ) and coherent phenomena such as Rabi flopping and Ramsey fringes. The protocol requires a single, far-off-resonant laser that is not specific to the molecule, so many other molecular ions, including polyatomic species, could be treated using the same methods in the same apparatus by changing the molecular source. Combined with the long interrogation times afforded by ion traps, a broad range of molecular ions could be studied with unprecedented control and precision. Our technique thus represents a critical step towards applications such as precision molecular spectroscopy, stringent tests of fundamental physics, quantum computing and precision control of molecular dynamics.

Kinetics and thermochemistry of polyatomic free radicals: New results and new understandings

NASA Technical Reports Server (NTRS)

Gutman, David; Slagle, Irene R.

1990-01-01

An experimental facility for the study of the chemical kinetics of polyatomic free radicals is described which consists of a heatable tubular reactor coupled to a photoionization mass spectrometer. Its use in different kinds of chemical kinetic studies is also discussed. Examples presented include studies of the C2H3 + O2, C2H3 + HC1, CH3 + O, and CH3 + CH3 reactions. The heat of formation of C2H3 was obtained from the results of the study of the C2H3 + HC1 reaction.

New Cs sputter ion source with polyatomic ion beams for secondary ion mass spectrometry applications

NASA Astrophysics Data System (ADS)

Belykh, S. F.; Palitsin, V. V.; Veryovkin, I. V.; Kovarsky, A. P.; Chang, R. J. H.; Adriaens, A.; Dowsett, M. G.; Adams, F.

2007-08-01

A simple design for a cesium sputter ion source compatible with vacuum and ion-optical systems as well as with electronics of the commercially available Cameca IMS-4f instrument is reported. This ion source has been tested with the cluster primary ions of Sin- and Cun-. Our experiments with surface characterization and depth profiling conducted to date demonstrate improvements of the analytical capabilities of the secondary ion mass spectrometry instrument due to the nonadditive enhancement of secondary ion emission and shorter ion ranges of polyatomic projectiles compared to atomic ones with the same impact energy.

Polyatomic interferences on high precision uranium isotope ratio measurements by MC-ICP-MS: Applications to environmental sampling for nuclear safeguards

DOE PAGES

Pollington, Anthony D.; Kinman, William S.; Hanson, Susan K.; ...

2015-09-04

Modern mass spectrometry and separation techniques have made measurement of major uranium isotope ratios a routine task; however accurate and precise measurement of the minor uranium isotopes remains a challenge as sample size decreases. One particular challenge is the presence of isobaric interferences and their impact on the accuracy of minor isotope 234U and 236U measurements. Furthermore, we present techniques used for routine U isotopic analysis of environmental nuclear safeguards samples and evaluate polyatomic interferences that negatively impact accuracy as well as methods to mitigate their impacts.

Fragmentation of Small Molecules by Photo-Double Ionization

NASA Astrophysics Data System (ADS)

Osipov, Timur

2008-05-01

Molecular structure, formation, breakup pathways and recombination formed the subject of many theoretical and experimental studies. Among molecular species like H2, CO, N2, O2 recently great attention has been paid to the dynamics of the fragmentations and rearrangements of C2H2 molecule. Nature's smallest stable hydrocarbon, the symmetric linear acetylene molecule, C2H2, is an important polyatomic system for the study of photo initiated processes. Important features of the intramolecular dynamics in neutral acetylene have been revealed over many years through numerous spectroscopic studies. More recently, the availability of synchrotron radiation and intense laser sources has lead to intriguing studies of the ionization, isomerization and breakup dynamics of acetylene ions. Of particular interest are the yields into the symmetric (CH^+/CH^+), deprotonation (HCC^+/H^+) and quasi-symmetric (HHC^+/C^+) channels, the latter involving isomerization from the neutral acetylene structure into the vinylidene configuration prior to breakup. One expects that the products of dissociation, their kinetic energy releases (KER) and the isomerization times will depend on the particular initial electronic states of the dication involved, but such detailed information has heretofore not been available. We will present the results of the experiment where the dication of acetylene is prepared by Auger decay following core-level X-ray photoionization. Cold Target Recoil Ion Momentum Spectroscopy technique was used to measure the corresponding 3d momentum vectors of Auger electrons and recoil ions in coincidence. We will show that this experimental approach, in combination with ab initio quantum mechanical calculations, can yield a comprehensive map of the two-body dissociation pathways including transition through different electronic energy surfaces, barriers to direct dissociation and the associated rearrangement channels. Work done in collaboration with T. Rescigno, T. Weber, S. Miyabe, M. Hertlein, B. Feinberg, M. Prior, and A. Belkacem, Lawrence Berkeley National Laboratory; T. Jahnke, O. Jagutzki, L. Schmidt, M. Sch"offler, L. Foucar, S. Sch"ossler, T. Havermeier, S. Voss, and R. D"orner, Institut fur Kernphysik, J. W. Goethe-Universitat Frankfurt am Main; A. Landers, Auburn University, Alabama; A. Alnaser, Kansas State University; and L. Cocke, Kansas State University.

Approximate first-principles anharmonic calculations of polyatomic spectra using MP2 and B3LYP potentials: comparisons with experiment.

PubMed

Roy, Tapta Kanchan; Carrington, Tucker; Gerber, R Benny

2014-08-21

Anharmonic vibrational spectroscopy calculations using MP2 and B3LYP computed potential surfaces are carried out for a series of molecules, and frequencies and intensities are compared with those from experiment. The vibrational self-consistent field with second-order perturbation correction (VSCF-PT2) is used in computing the spectra. The test calculations have been performed for the molecules HNO3, C2H4, C2H4O, H2SO4, CH3COOH, glycine, and alanine. Both MP2 and B3LYP give results in good accord with experimental frequencies, though, on the whole, MP2 gives very slightly better agreement. A statistical analysis of deviations in frequencies from experiment is carried out that gives interesting insights. The most probable percentage deviation from experimental frequencies is about -2% (to the red of the experiment) for B3LYP and +2% (to the blue of the experiment) for MP2. There is a higher probability for relatively large percentage deviations when B3LYP is used. The calculated intensities are also found to be in good accord with experiment, but the percentage deviations are much larger than those for frequencies. The results show that both MP2 and B3LYP potentials, used in VSCF-PT2 calculations, account well for anharmonic effects in the spectroscopy of molecules of the types considered.

Theoretical study of the vibrational relaxation of the methyl radical in collisions with helium

NASA Astrophysics Data System (ADS)

Ma, Qianli; Dagdigian, Paul J.; Alexander, Millard H.

2013-03-01

We report a theoretical investigation of the relaxation of the umbrella vibrational mode (the ν2 mode) of the CH3 molecule in its ground tilde{X}^2A_2^' ' } electronic state in collisions with helium. We have calculated a four-dimensional potential energy surface (PES) for the interaction between CH3 with different umbrella displacements and a helium atom, using a restricted open-shell coupled-cluster method with inclusion of all single, double, and (perturbatively) triple excitations [RCCSD(T)]. With this PES we carried out full close-coupling scattering calculations including all CH3 umbrella-rotational levels with v2 ⩽ 3. To our knowledge, this work represents the first fully quantum calculations of ro-vibrational relaxation of a polyatomic. In more detail, we investigate propensities in the calculated ro-vibrational cross sections and the dependence on initial rotational excitation, as well as determining thermal rate constants. Overall, ro-vibrational relaxation is nearly two orders of magnitude less efficient than pure-rotational relaxation, with a noticeable dependence on the initial rotational level. We predict the room temperature v2 = 1 vibrational relaxation rate constant to be 5.4 × 10-12 cm3 molecule-1 s-1, compared to the rate constants for pure-rotational relaxation of the lower rotational levels (˜2.0 × 10-10 cm3 molecule-1 s-1).

An Update on the Non-Mass-Dependent Isotope Fractionation under Thermal Gradient

NASA Technical Reports Server (NTRS)

Sun, Tao; Niles, Paul; Bao, Huiming; Socki, Richard; Liu, Yun

2013-01-01

Mass flow and compositional gradient (elemental and isotope separation) occurs when flu-id(s) or gas(es) in an enclosure is subjected to a thermal gradient, and the phenomenon is named thermal diffusion. Gas phase thermal diffusion has been theoretically and experimentally studied for more than a century, although there has not been a satisfactory theory to date. Nevertheless, for isotopic system, the Chapman-Enskog theory predicts that the mass difference is the only term in the thermal diffusion separation factors that differs one isotope pair to another,with the assumptions that the molecules are spherical and systematic (monoatomic-like structure) and the particle collision is elastic. Our previous report indicates factors may be playing a role because the Non-Mass Dependent (NMD) effect is found for both symmetric and asymmetric, linear and spherical polyatomic molecules over a wide range of temperature (-196C to +237C). The observed NMD phenomenon in the simple thermal-diffusion experiments demands quantitative validation and theoretical explanation. Besides the pressure and temperature dependency illustrated in our previous reports, efforts are made in this study to address issues such as the role of convection or molecular structure and whether it is a transient, non-equilibrium effect only.

Predicting absorption and dispersion in acoustics by direct simulation Monte Carlo: Quantum and classical models for molecular relaxation.

PubMed

Hanford, Amanda D; O'Connor, Patrick D; Anderson, James B; Long, Lyle N

2008-06-01

In the current study, real gas effects in the propagation of sound waves are simulated using the direct simulation Monte Carlo method for a wide range of frequencies. This particle method allows for treatment of acoustic phenomena at high Knudsen numbers, corresponding to low densities and a high ratio of the molecular mean free path to wavelength. Different methods to model the internal degrees of freedom of diatomic molecules and the exchange of translational, rotational and vibrational energies in collisions are employed in the current simulations of a diatomic gas. One of these methods is the fully classical rigid-rotor/harmonic-oscillator model for rotation and vibration. A second method takes into account the discrete quantum energy levels for vibration with the closely spaced rotational levels classically treated. This method gives a more realistic representation of the internal structure of diatomic and polyatomic molecules. Applications of these methods are investigated in diatomic nitrogen gas in order to study the propagation of sound and its attenuation and dispersion along with their dependence on temperature. With the direct simulation method, significant deviations from continuum predictions are also observed for high Knudsen number flows.

Dynamical tunneling versus fast diffusion for a non-convex Hamiltonian

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pittman, S. M.; Tannenbaum, E.; Heller, E. J.

This paper attempts to resolve the issue of the nature of the 0.01-0.1 cm{sup −1} peak splittings observed in high-resolution IR spectra of polyatomic molecules. One hypothesis is that these splittings are caused by dynamical tunneling, a quantum-mechanical phenomenon whereby energy flows between two disconnected regions of phase-space across dynamical barriers. However, a competing classical mechanism for energy flow is Arnol’d diffusion, which connects different regions of phase-space by a resonance network known as the Arnol’d web. The speed of diffusion is bounded by the Nekhoroshev theorem, which guarantees stability on exponentially long time scales if the Hamiltonian is steep.more » Here we consider a non-convex Hamiltonian that contains the characteristics of a molecular Hamiltonian, but does not satisfy the Nekhoroshev theorem. The diffusion along the Arnol’d web is expected to be fast for a non-convex Hamiltonian. While fast diffusion is an unlikely competitor for longtime energy flow in molecules, we show how dynamical tunneling dominates compared to fast diffusion in the nearly integrable regime for a non-convex Hamiltonian, as well as present a new kind of dynamical tunneling.« less

Construction of reactive potential energy surfaces with Gaussian process regression: active data selection

NASA Astrophysics Data System (ADS)

Guan, Yafu; Yang, Shuo; Zhang, Dong H.

2018-04-01

Gaussian process regression (GPR) is an efficient non-parametric method for constructing multi-dimensional potential energy surfaces (PESs) for polyatomic molecules. Since not only the posterior mean but also the posterior variance can be easily calculated, GPR provides a well-established model for active learning, through which PESs can be constructed more efficiently and accurately. We propose a strategy of active data selection for the construction of PESs with emphasis on low energy regions. Through three-dimensional (3D) example of H3, the validity of this strategy is verified. The PESs for two prototypically reactive systems, namely, H + H2O ↔ H2 + OH reaction and H + CH4 ↔ H2 + CH3 reaction are reconstructed. Only 920 and 4000 points are assembled to reconstruct these two PESs respectively. The accuracy of the GP PESs is not only tested by energy errors but also validated by quantum scattering calculations.

Interference in acetylene intersystem crossing acts as the molecular analog of Young's double-slit experiment

PubMed Central

de Groot, Mattijs; Field, Robert W.; Buma, Wybren J.

2009-01-01

We report on an experimental approach that reveals crucial details of the composition of singlet-triplet mixed eigenstates in acetylene. Intersystem crossing in this prototypical polyatomic molecule embodies the mixing of the lowest excited singlet state (S1) with 3 triplet states (T1, T2, and T3). Using high-energy (157-nm) photons from an F2 laser to record excited-state photoelectron spectra, we have decomposed the mixed eigenstates into their S1, T3, T2, and T1 constituent parts. One example of the interpretive power that ensues from the selective sensitivity of the experiment to the individual electronic state characters is the discovery and examination of destructive interference between two doorway-mediated intersystem crossing pathways. This observation of an interference effect in nonradiative decay opens up possibilities for rational coherent control over molecular excited state dynamics. PMID:19179288

DOE Office of Scientific and Technical Information (OSTI.GOV)

Witte, Travis

This dissertation provides a general introduction to Inductively coupled plasma-mass spectrometry (ICP-MS) and laser ablation (LA) sampling, with an examination of analytical challenges in the employment of this technique. It discusses the origin of metal oxide ions (MO+) in LA-ICP-MS, as well as the effect of introducing helium and nitrogen to the aerosol gas flow on the formation of these polyatomic interferences. It extends the study of polyatomic ions in LA-ICP-MS to metal argide (MAr+) species, an additional source of possible significant interferences in the spectrum. It describes the application of fs-LA-ICP-MS to the determination of uranium isotope ratios inmore » particulate samples.« less

Some possibilities of using gas mixtures other than air in aerodynamic research

NASA Technical Reports Server (NTRS)

Chapman, Dean R

1956-01-01

A study is made of the advantages that can be realized in compressible-flow research by employing a substitute heavy gas in place of air. The present report is based on the idea that by properly mixing a heavy monatomic gas with a suitable heavy polyatomic gas, it is possible to obtain a heavy gas mixture which has the correct ratio of specific heats and which is nontoxic, nonflammable, thermally stable, chemically inert, and comprised of commercially available components. Calculations were made of wind-tunnel characteristics for 63 gas pairs comprising 21 different polyatomic gases properly mixed with each of three monatomic gases (argon, krypton, and zenon).

Metal-assisted SIMS and cluster ion bombardment for ion yield enhancement

NASA Astrophysics Data System (ADS)

Heile, A.; Lipinsky, D.; Wehbe, N.; Delcorte, A.; Bertrand, P.; Felten, A.; Houssiau, L.; Pireaux, J.-J.; De Mondt, R.; Van Vaeck, L.; Arlinghaus, H. F.

2008-12-01

In addition to structural information, a detailed knowledge of the local chemical environment proves to be of ever greater importance, for example for the development of new types of materials as well as for specific modifications of surfaces and interfaces in multiple fields of materials science or various biomedical and chemical applications. But the ongoing miniaturization and therefore reduction of the amount of material available for analysis constitute a challenge to the detection limits of analytical methods. In the case of time-of-flight secondary ion mass spectrometry (TOF-SIMS), several methods of secondary ion yield enhancement have been proposed. This paper focuses on the investigation of the effects of two of these methods, metal-assisted SIMS and polyatomic primary ion bombardment. For this purpose, thicker layers of polystyrene (PS), both pristine and metallized with different amounts of gold, were analyzed using monoatomic (Ar +, Ga +, Xe +, Bi +) and polyatomic (SF 5+, Bi 3+, C 60+) primary ions. It was found that polyatomic ions generally induce a significant increase of the secondary ion yield. On the other hand, with gold deposition, a yield enhancement can only be detected for monoatomic ion bombardment.

Theoretical investigation of gas-surface interactions

NASA Technical Reports Server (NTRS)

Dyall, Kenneth G.

1992-01-01

The investigation into the appearance of intruder states from the negative continuum when some of the two-electron integrals were omitted was completed. The work shows that, provided all integrals involving core contracted functions in an atomic general contraction are included, or that the core functions are radially localized, meaningful results are obtained and intruder states do not appear. In the area of program development, the Dirac-Hartree-Fock (DHF) program for closed-shell polyatomic molecules was extended to permit Kramers-restricted open-shell DHF calculations with one electron in an open shell or one hole in a closed shell, or state-averaged DHF calculations over several particle or hole doublet states. One application of the open-shell code was to the KO molecule. Another major area of program development is the transformation of integrals from the scalar basis in which they are generated to the 2-spinor basis employed in parts of the DHF program, and hence to supermatrix form. Particularly concerning the omission of small component integrals, and with increase in availability of disk space, it is now possible to consider transforming the integrals. The use of ordered integrals, either in the scalar basis or in the 2-spinor basis, would considerably speed up the construction of the Fock matrix, and even more so if supermatrices were constructed. A considerable amount of effort was spent on analyzing the integral ordering and tranformation for the DHF program. The work of assessing the reliability of the relativistic effective core potentials (RECPs) was continued with calculation of the group IV monoxides. The perturbation of the metal atom provided by oxygen is expected to be larger than that provided by hydrogen and thus provide a better test of the qualification of the RECPs. Calculations on some platinum hydrides were carried out at nonrelativistic (NR), perturbation theory (PT) and DHF levels. Reprints of four papers describing this work are included.

Predicting Bond Dissociation Energies of Transition-Metal Compounds by Multiconfiguration Pair-Density Functional Theory and Second-Order Perturbation Theory Based on Correlated Participating Orbitals and Separated Pairs.

PubMed

Bao, Junwei Lucas; Odoh, Samuel O; Gagliardi, Laura; Truhlar, Donald G

2017-02-14

We study the performance of multiconfiguration pair-density functional theory (MC-PDFT) and multireference perturbation theory for the computation of the bond dissociation energies in 12 transition-metal-containing diatomic molecules and three small transition-metal-containing polyatomic molecules and in two transition-metal dimers. The first step is a multiconfiguration self-consistent-field calculation, for which two choices must be made: (i) the active space and (ii) its partition into subspaces, if the generalized active space formulation is used. In the present work, the active space is chosen systematically by using three correlated-participating-orbitals (CPO) schemes, and the partition is chosen by using the separated-pair (SP) approximation. Our calculations show that MC-PDFT generally has similar accuracy to CASPT2, and the active-space dependence of MC-PDFT is not very great for transition-metal-ligand bond dissociation energies. We also find that the SP approximation works very well, and in particular SP with the fully translated BLYP functional SP-ftBLYP is more accurate than CASPT2. SP greatly reduces the number of configuration state functions relative to CASSCF. For the cases of FeO and NiO with extended-CPO active space, for which complete active space calculations are unaffordable, SP calculations are not only affordable but also of satisfactory accuracy. All of the MC-PDFT results are significantly better than the corresponding results with broken-symmetry spin-unrestricted Kohn-Sham density functional theory. Finally we test a perturbation theory method based on the SP reference and find that it performs slightly worse than CASPT2 calculations, and for most cases of the nominal-CPO active space, the approximate SP perturbation theory calculations are less accurate than the much less expensive SP-PDFT calculations.

Ultrafast photochemistry of polyatomic molecules containing labile halogen atoms in solution

NASA Astrophysics Data System (ADS)

Mereshchenko, Andrey S.

Because breaking and making of chemical bonds lies at the heart of chemistry, this thesis focuses on dynamic studies of labile molecules in solutions using ultrafast transient absorption spectroscopy. Specifically, my interest is two-fold: (i) novel reaction intermediates of polyhalogenated carbon, boron and phosphorus compounds; (ii) photophysics and photochemistry of labile copper(II) halide complexes. Excitation of CH2Br2, CHBr3, BBr 3, and PBr3 into n(Br)sigma*(X-Br) states, where X=C, B, or P, leads to direct photoisomerization with formation of isomers having Br-Br bonds as well as rupture of one of X-Br bonds with the formation of a Br atom and a polyatomic radical fragment, which subsequently recombine to form similar isomer products. Nonpolar solvation stabilizes the isomers, consistent with intrinsic reaction coordinate calculations of the isomer ground state potential energy surfaces at the density functional level of theory, and consequently, the involvement of these highly energetic species on chemically-relevant time scales needs to be taken into account. Monochlorocomplexes in methanol solutions promoted to the ligand-to-metal charge transfer (LMCT) excited state predominantly undergo internal conversion via back electron transfer, giving rise to vibrationally hot ground-state parent complexes. Copper-chloride homolitical bond dissociation yielding the solvated copper(I) and Cl- atom/solvent CT complexes constitutes a minor pathway. Insights into ligand substitution mechanisms were acquired by monitoring the recovery of monochloro complexes at the expense of two unexcited dichloro- and unsubstituted forms of Cu(II) complexes also present in the solution. Detailed description of ultrafast excited-state dynamics of CuCl 42- complexes in acetonitrile upon excitation into all possible Ligand Field (LF) excited states and two most intense LMCT transitions is reported. The LF states were found to be nonreactive with lifetimes remarkably longer than those for copper(II) complexes studied so far, in particular, copper blue proteins. The highest 2A1 and lowest 2E LF states relax directly to the ground electronic state whereas the intermediate 2B1 LF state relaxes stepwise through the 2E state. The LMCT excited states are short-lived undergoing either ionic dissociation (CuCl3- + Cl-) or cascading relaxation through the manifold of vibrationally hot LF states to the ground state.

High-Resolution Laser Spectroscopy of Free Radicals in Nearly Degenerate Electronic States

NASA Astrophysics Data System (ADS)

Liu, Jinjun

2017-06-01

Rovibronic structure of molecules in orbitally degenerate electronic states including Renner-Teller (RT) and Jahn-Teller (JT) active molecules has been extensively studied. Less is known about rotational structure of polyatomic molecules in nearly degenerate states, especially those with low (e.g., C_s) symmetry that are subject to the pseudo-Jahn-Teller (pJT) effect. In the case of free radicals, the unpaired electron further complicates energy levels by inducing spin-orbit (SO) and spin-rotation (SR) splittings. Asymmetric deuteration or methyl substitution of C_{3v} free radicals such as CH_3O, CaCH_3, and CaOCH_3 lowers the molecular symmetry, lifts the vibronic degeneracy, and reduces the JT effect to the pJT effect. New spectroscopic models are required to reproduce the rovibronic structure and simulate the experimentally obtained spectra of pJT-active free radicals. It has been found that rotational and fine-structure analysis of spectra involving nearly degenerate states may aid in vibronic analysis and interpretation of effective molecular constants. Especially, SO and Coriolis interactions that couple the two states can be determined accurately from fitting the experimental spectra. Coupling between the two electronic states also affects the intensities of rotational and vibronic transitions. The study on free radicals in nearly degenerate states provides a promising avenue of research which may bridge the gap between symmetry-induced degenerate states and the Born-Oppenheimer (BO) limit of unperturbed electronic states.

Three milieux for interstellar chemistry: gas, dust, and ice

NASA Astrophysics Data System (ADS)

Herbst, Eric

The interdisciplinary science of astrochemistry is 45 years of age, if we pinpoint its origin to have occurred when the first polyatomic molecules were detected in the interstellar gas. Since that time, the field has grown remarkably from an esoteric area of research to one that unites scientists around the globe. Almost 200 different molecules have been detected in the gas-phase of interstellar clouds, mainly by rotational spectroscopy, while dust particles and their icy mantles in colder regions can be probed by vibrational spectroscopy. Astrochemistry is exciting to scientists in a number of different fields. Astronomers are interested in molecular spectra from the heavens because such spectra are excellent probes of the physical conditions where molecules exist, while chemists are interested in the exotic molecules, their spectra, and the unusual chemical processes that produce and destroy them under conditions often very different from those on our home planet. Chemical simulations involving thousands of reactions are now used to calculate concentrations and spectra of interstellar molecules as functions of time. Even biologists share an interest in the subject, because the interstellar clouds of gas and dust, portions of which collapse to form stars and planetary systems, contain organic molecules that may become part of the initial inventory of new planets and may indeed be the precursors of life. An irresistible subject to its practitioners, astrochemistry is proving to be exciting to a much wider audience. In this perspective article, the field is first introduced, and the emphasis is then placed on the three environments in which chemistry occurs in the interstellar medium: the gas phase, the surfaces of bare dust particles, and the ice mantles that cover bare grains in cold dense interstellar clouds. What we do know and what we do not know is distinguished. The status of chemical simulations for a variety of interstellar sources having to do with stellar and planetary evolution is surveyed. An optimistic view of the future of astrochemistry ends the article.

Luminous phenomena and electromagnetic VHF wave emission originated from earthquake-related radon exhalation

NASA Astrophysics Data System (ADS)

Seki, A.; Tobo, I.; Omori, Y.; Muto, J.; Nagahama, H.

2013-12-01

Anomalous luminous phenomena and electromagnetic wave emission before or during earthquakes have been reported (e.g., the 1965 Matsushiro earthquake swarm). However, their mechanism is still unsolved, in spite of many models for these phenomena. Here, we propose a new model about luminous phenomena and electromagnetic wave emission during earthquake by focusing on atmospheric radon (Rn-222) and its daughter nuclides (Po-218 and Po-214). Rn-222, Po-218 and Po-214 are alpha emitters, and these alpha particles ionize atmospheric molecules. A light emission phenomenon, called 'the air luminescence', is caused by de-excitation of the ionized molecules of atmospheric nitrogen due to electron impact ionization from alpha particles. The de-excitation is from the second positive system of neutral nitrogen molecules and the first negative system of nitrogen molecule ion. Wavelengths of lights by these transitions include the visible light wavelength. So based on this mechanism, we proposed a new luminous phenomenon model before or during earthquake: 1. The concentration of atmospheric radon and its daughter nuclides increase anomalously before or during earthquakes, 2. Nitrogen molecules and their ions are excited by alpha particles emitted from Rn-222, Po-218 and Po-214, and air luminescence is generated by their de-excitation. Similarly, electromagnetic VHF wave emission can be explained by ionizing effect of radon and its daughter nuclides. Boyarchuk et al. (2005) proposed a model that electromagnetic VHF wave emission is originated when excited state of neutral clusters changes. Radon gas ionizes atmosphere and forms positively and negatively charged heavy particles. The process of ion hydration in ordinary air can be determined by the formation of complex chemically active structures of the various types of ion radicals. As a result of the association of such hydration radical ions, a neutral cluster, which is dipole quasi-molecules, is formed. A neutral cluster's rotation-rotation transition causes electromagnetic VHF wave emission. We also discuss a possibility of electromagnetic VHF wave emission from excitation of polyatomic molecules by alpha particles from Rn-222 and its daughter nuclides, similar to air luminescence by excitation of nitrogen molecule in the viewpoint of electromagnetic radiation in quantum theory.

A spherical electron cloud hopping model for studying product branching ratios of dissociative recombination.

PubMed

Yu, Hua-Gen

2008-05-21

A spherical electron cloud hopping (SECH) model is proposed to study the product branching ratios of dissociative recombination (DR) of polyatomic systems. In this model, the fast electron-captured process is treated as an instantaneous hopping of a cloud of uniform spherical fractional point charges onto a target M+q ion (or molecule). The sum of point charges (-1) simulates the incident electron. The sphere radius is determined by a critical distance (Rc eM) between the incoming electron (e-) and the target, at which the potential energy of the e(-)-M+q system is equal to that of the electron-captured molecule M+q(-1) in a symmetry-allowed electronic state with the same structure as M(+q). During the hopping procedure, the excess energies of electron association reaction are dispersed in the kinetic energies of M+q(-1) atoms to conserve total energy. The kinetic energies are adjusted by linearly adding atomic momenta in the direction of driving forces induced by the scattering electron. The nuclear dynamics of the resultant M+q(-1) molecule are studied by using a direct ab initio dynamics method on the adiabatic potential energy surface of M+q(-1), or together with extra adiabatic surface(s) of M+q(-1). For the latter case, the "fewest switches" surface hopping algorithm of Tully was adapted to deal with the nonadiabaticity in trajectory propagations. The SECH model has been applied to study the DR of both CH+ and H3O+(H2O)2. The theoretical results are consistent with the experiment. It was found that water molecules play an important role in determining the product branching ratios of the molecular cluster ion.

Rational extended thermodynamics of a rarefied polyatomic gas with molecular relaxation processes

NASA Astrophysics Data System (ADS)

Arima, Takashi; Ruggeri, Tommaso; Sugiyama, Masaru

2017-10-01

We present a more refined version of rational extended thermodynamics of rarefied polyatomic gases in which molecular rotational and vibrational relaxation processes are treated individually. In this case, we need a triple hierarchy of the moment system and the system of balance equations is closed via the maximum entropy principle. Three different types of the production terms in the system, which are suggested by a generalized BGK-type collision term in the Boltzmann equation, are adopted. In particular, the rational extended thermodynamic theory with seven independent fields (ET7) is analyzed in detail. Finally, the dispersion relation of ultrasonic wave derived from the ET7 theory is confirmed by the experimental data for CO2, Cl2, and Br2 gases.

Kinetic theory of two-temperature polyatomic plasmas

NASA Astrophysics Data System (ADS)

Orlac'h, Jean-Maxime; Giovangigli, Vincent; Novikova, Tatiana; Roca i Cabarrocas, Pere

2018-03-01

We investigate the kinetic theory of two-temperature plasmas for reactive polyatomic gas mixtures. The Knudsen number is taken proportional to the square root of the mass ratio between electrons and heavy-species, and thermal non-equilibrium between electrons and heavy species is allowed. The kinetic non-equilibrium framework also requires a weak coupling between electrons and internal energy modes of heavy species. The zeroth-order and first-order fluid equations are derived by using a generalized Chapman-Enskog method. Expressions for transport fluxes are obtained in terms of macroscopic variable gradients and the corresponding transport coefficients are expressed as bracket products of species perturbed distribution functions. The theory derived in this paper provides a consistent fluid model for non-thermal multicomponent plasmas.

Applications of a general random-walk theory for confined diffusion.

PubMed

Calvo-Muñoz, Elisa M; Selvan, Myvizhi Esai; Xiong, Ruichang; Ojha, Madhusudan; Keffer, David J; Nicholson, Donald M; Egami, Takeshi

2011-01-01

A general random walk theory for diffusion in the presence of nanoscale confinement is developed and applied. The random-walk theory contains two parameters describing confinement: a cage size and a cage-to-cage hopping probability. The theory captures the correct nonlinear dependence of the mean square displacement (MSD) on observation time for intermediate times. Because of its simplicity, the theory also requires modest computational requirements and is thus able to simulate systems with very low diffusivities for sufficiently long time to reach the infinite-time-limit regime where the Einstein relation can be used to extract the self-diffusivity. The theory is applied to three practical cases in which the degree of order in confinement varies. The three systems include diffusion of (i) polyatomic molecules in metal organic frameworks, (ii) water in proton exchange membranes, and (iii) liquid and glassy iron. For all three cases, the comparison between theory and the results of molecular dynamics (MD) simulations indicates that the theory can describe the observed diffusion behavior with a small fraction of the computational expense. The confined-random-walk theory fit to the MSDs of very short MD simulations is capable of accurately reproducing the MSDs of much longer MD simulations. Furthermore, the values of the parameter for cage size correspond to the physical dimensions of the systems and the cage-to-cage hopping probability corresponds to the activation barrier for diffusion, indicating that the two parameters in the theory are not simply fitted values but correspond to real properties of the physical system.

Atomic and polyatomic molecules at metal surfaces studied by synchrotron far-IR RAIRS

NASA Astrophysics Data System (ADS)

Raval, Rasmita; Roberts, Adam J.; Williams, Jamie; Nunney, Timothy S.; Surman, Mark

1997-10-01

Far-IR Reflection Absorption Infrared Spectroscopy (RAIRS) has been used to probe submonolayers of adsorbates created under clean controlled conditions on small area single crystal surfaces, using the newly commissioned Daresbury 13.3 Far-IR synchrotron beamline. Adsorbed formate species on Cu(110) were studied as an example of an adsorbate for which a large structural data-base already exists in the literature from other surface science techniques. Our high resolution Far-IR data has allowed two distinct vCu-O vibrations to be monitored for 0.25 monolayer of formate adsorbed on Cu(110) at 300 K. We rule out a lower symmetry formate complex giving rise to these vibrations and, instead, attribute the two bands to at least two chemically distinct species at the surface, a possibility that has hitherto not been included in the analyses of this system using other techniques. In addition, we also report the first RAIRS spectrum of the vCu-O stretching vibration for adsorbed atomic O on the Cu(110) surface at 300 K. The dissociative adsorption of oxygen, at room temperature, on this surface is known to induce a massive reconstruction of the surface in which `added' rows of Cu-O-Cu strings form on the surface in the [001] direction to give rise to the (1 X 2) missing row structure. The vCu-O vibration frequency is found to be invariant as a function of coverage, suggesting that the chemical nature of the Cu-O-Cu entity remains essentially unaltered during the growth of the reconstructed phase.

Identifying the Tunneling Site in Strong-Field Ionization of H_{2}^{+}.

PubMed

Liu, Kunlong; Barth, Ingo

2017-12-15

The tunneling site of the electron in a molecule exposed to a strong laser field determines the initial position of the ionizing electron and, as a result, has a large impact on the subsequent ultrafast electron dynamics on the polyatomic Coulomb potential. Here, the tunneling site of the electron of H_{2}^{+} ionized by a strong circularly polarized (CP) laser pulse is studied by numerically solving the time-dependent Schrödinger equation. We show that the electron removed from the down-field site is directly driven away by the CP field and the lateral photoelectron momentum distribution (LPMD) exhibits a Gaussian-like distribution, whereas the corresponding LPMD of the electron removed from the up-field site differs from the Gaussian shape due to the Coulomb focusing and scattering by the down-field core. Our current study presents the direct evidence clarifying a long-standing controversy over the tunneling site in H_{2}^{+} and raises the important role of the tunneling site in strong-field molecular ionization.

Quantum and classical dynamics of water dissociation on Ni(111): A test of the site-averaging model in dissociative chemisorption of polyatomic molecules

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jiang, Bin; Department of Chemical Physics, University of Science and Technology of China, Hefei 230026; Guo, Hua, E-mail: hguo@unm.edu

Recently, we reported the first highly accurate nine-dimensional global potential energy surface (PES) for water interacting with a rigid Ni(111) surface, built on a large number of density functional theory points [B. Jiang and H. Guo, Phys. Rev. Lett. 114, 166101 (2015)]. Here, we investigate site-specific reaction probabilities on this PES using a quasi-seven-dimensional quantum dynamical model. It is shown that the site-specific reactivity is largely controlled by the topography of the PES instead of the barrier height alone, underscoring the importance of multidimensional dynamics. In addition, the full-dimensional dissociation probability is estimated by averaging fixed-site reaction probabilities with appropriatemore » weights. To validate this model and gain insights into the dynamics, additional quasi-classical trajectory calculations in both full and reduced dimensions have also been performed and important dynamical factors such as the steering effect are discussed.« less

The effects of focusing power on TEA CO2 laser-induced gas breakdown and the consequent pulse shaping effects

NASA Astrophysics Data System (ADS)

Beheshtipour, Saleheh; Safari, Ebrahim; Majdabadi, Abbas; Silakhori, Kaveh

2018-02-01

Transversely Excited Atmospheric (TEA) CO2 laser pulses were used in order to generate an optical breakdown in a variety of mono- and polyatomic molecules using different focusing powers. The dependence of the spark kernel geometry and the transmitted pulse shapes on the focusing power as well as the pressure, molecular weight, and ionization energy of the gases was investigated in detail. Partial removal of the transmitted pulse tail in the 0.05-2.6 μs range together with shortened spikes in the 10-60 ns range has been observed by applying a 2.5 cm focal length lens for all the gases. At higher focal lengths, this effect is only incompletely observed for He gas. Spatial-temporal analyses of the laser beams and the relevant plasma plumes indicate that this behavior is due to the drop in the plasma density below the critical level, before the laser pulse tail is completed.

HO2 rovibrational eigenvalue studies for nonzero angular momentum

NASA Astrophysics Data System (ADS)

Wu, Xudong T.; Hayes, Edward F.

1997-08-01

An efficient parallel algorithm is reported for determining all bound rovibrational energy levels for the HO2 molecule for nonzero angular momentum values, J=1, 2, and 3. Performance tests on the CRAY T3D indicate that the algorithm scales almost linearly when up to 128 processors are used. Sustained performance levels of up to 3.8 Gflops have been achieved using 128 processors for J=3. The algorithm uses a direct product discrete variable representation (DVR) basis and the implicitly restarted Lanczos method (IRLM) of Sorensen to compute the eigenvalues of the polyatomic Hamiltonian. Since the IRLM is an iterative method, it does not require storage of the full Hamiltonian matrix—it only requires the multiplication of the Hamiltonian matrix by a vector. When the IRLM is combined with a formulation such as DVR, which produces a very sparse matrix, both memory and computation times can be reduced dramatically. This algorithm has the potential to achieve even higher performance levels for larger values of the total angular momentum.

Photophysical behavior of polyatomic molecules

NASA Astrophysics Data System (ADS)

Ware, W. R.

1980-10-01

Part one of this report deals with attempts over the past several years to devise a more sophisticated theory of diffusion controlled reactions than that presented by Collins and Kimball. In particular, the investigators were interested in a more realistic formulation of the problem of high concentration quenching where quenches in the vicinity of the molecular to be quenched must be considered. It was desired however, to obtain a formalism which was tractable mathematically and which contained parameters which would be related to experiment. Part two deals with the photophysics of systems exhibiting molecular association both in the ground and excited states has been studied. The emphasis has been on kinetic models, the measurement of rate constants associated with these models, and the determination of activation parameters and equilibrium thermodynamic parameters associated with the exciplex formation and disappearance. Studies of solvent effects and steric effects on the behavior of exciplex systems have been carried out. The case of rapid equilibrium where the monomer and exciplex decay with the same rate constant has also been examined.

Static time-of-flight secondary ion mass spectrometry analysis of microelectronics related substrates using a polyatomic ion source

NASA Astrophysics Data System (ADS)

Ravanel, X.; Trouiller, C.; Juhel, M.; Wyon, C.; Kwakman, L. F. Tz.; Léonard, D.

2008-12-01

Recent time-of-flight secondary ion mass spectrometry studies using primary ion cluster sources such as Au n+, SF 5+, Bi n+ or C 60+ have shown the great advantages in terms of secondary ion yield enhancement and ion formation efficiency of polyatomic ion sources as compared to monoatomic ion sources like the commonly used Ga +. In this work, the effective gains provided by such a source in the static ToF-SIMS analysis of microelectronics devices were investigated. Firstly, the influence of the number of atoms in the primary cluster ion on secondary ion formation was studied for physically adsorbed di-isononyl phthalate (DNP) (plasticizer) and perfluoropolyether (PFPE). A drastic increase in secondary ion formation efficiency and a much lower detection limit were observed when using a polyatomic primary ion. Moreover, the yield of the higher mass species was much enhanced indicating a lower degree of fragmentation that can be explained by the fact that the primary ion energy is spread out more widely, or that there is a lower energy per incoming ion. Secondly, the influence of the number of Bi atoms in the Bi n primary ion on the information depth was studied using reference thermally grown silicon oxide samples. The information depth provided by a Bi n cluster was shown to be lowered when the number of atoms in the aggregate was increased.

Nicholas Metropolis Award for Outstanding Doctoral Thesis Work in Computational Physics: Quantum many-body physics of ultracold molecules in optical lattices: models and simulation methods

NASA Astrophysics Data System (ADS)

Wall, Michael

2014-03-01

Experimental progress in generating and manipulating synthetic quantum systems, such as ultracold atoms and molecules in optical lattices, has revolutionized our understanding of quantum many-body phenomena and posed new challenges for modern numerical techniques. Ultracold molecules, in particular, feature long-range dipole-dipole interactions and a complex and selectively accessible internal structure of rotational and hyperfine states, leading to many-body models with long range interactions and many internal degrees of freedom. Additionally, the many-body physics of ultracold molecules is often probed far from equilibrium, and so algorithms which simulate quantum many-body dynamics are essential. Numerical methods which are to have significant impact in the design and understanding of such synthetic quantum materials must be able to adapt to a variety of different interactions, physical degrees of freedom, and out-of-equilibrium dynamical protocols. Matrix product state (MPS)-based methods, such as the density-matrix renormalization group (DMRG), have become the de facto standard for strongly interacting low-dimensional systems. Moreover, the flexibility of MPS-based methods makes them ideally suited both to generic, open source implementation as well as to studies of the quantum many-body dynamics of ultracold molecules. After introducing MPSs and variational algorithms using MPSs generally, I will discuss my own research using MPSs for many-body dynamics of long-range interacting systems. In addition, I will describe two open source implementations of MPS-based algorithms in which I was involved, as well as educational materials designed to help undergraduates and graduates perform research in computational quantum many-body physics using a variety of numerical methods including exact diagonalization and static and dynamic variational MPS methods. Finally, I will mention present research on ultracold molecules in optical lattices, such as the exploration of many-body physics with polyatomic molecules, and the next generation of open source matrix product state codes. This work was performed in the research group of Prof. Lincoln D. Carr.

Simplified model to describe the dissociative recombination of linear polyatomic ions of astrophysical interest

NASA Astrophysics Data System (ADS)

Douguet, N.; Fonseca dos Santos, S.; Kokoouline, V.; Orel, A. E.

2015-01-01

We present results of a theoretical study on dissociative recombination of the HCNH+, HCO+ and N2H+ linear polyatomic ions at low energies using a simple theoretical model. In the present study, the indirect mechanism for recombination proceeds through the capture of the incoming electron in excited vibrational Rydberg states attached to the degenerate transverse modes of the linear ions. The strength of the non-adiabatic coupling responsible for dissociative recombination is determined directly from the near-threshold scattering matrix obtained numerically using the complex Kohn variational method. The final cross sections for the process are compared with available experimental data. It is demonstrated that at low collision energies, the major contribution to the dissociative recombination cross section is due to the indirect mechanism.

A BGK model for reactive mixtures of polyatomic gases with continuous internal energy

NASA Astrophysics Data System (ADS)

Bisi, M.; Monaco, R.; Soares, A. J.

2018-03-01

In this paper we derive a BGK relaxation model for a mixture of polyatomic gases with a continuous structure of internal energies. The emphasis of the paper is on the case of a quaternary mixture undergoing a reversible chemical reaction of bimolecular type. For such a mixture we prove an H -theorem and characterize the equilibrium solutions with the related mass action law of chemical kinetics. Further, a Chapman-Enskog asymptotic analysis is performed in view of computing the first-order non-equilibrium corrections to the distribution functions and investigating the transport properties of the reactive mixture. The chemical reaction rate is explicitly derived at the first order and the balance equations for the constituent number densities are derived at the Euler level.

Progress Towards a High-Precision Infrared Spectroscopic Survey of the H_3^+ Ion

NASA Astrophysics Data System (ADS)

Perry, Adam J.; Hodges, James N.; Markus, Charles R.; Kocheril, G. Stephen; Jenkins, Paul A., II; McCall, Benjamin J.

2015-06-01

The trihydrogen cation, H_3^+, represents one of the most important and fundamental molecular systems. Having only two electrons and three nuclei, H_3^+ is the simplest polyatomic system and is a key testing ground for the development of new techniques for calculating potential energy surfaces and predicting molecular spectra. Corrections that go beyond the Born-Oppenheimer approximation, including adiabatic, non-adiabatic, relativistic, and quantum electrodynamic corrections are becoming more feasible to calculate. As a result, experimental measurements performed on the H_3^+ ion serve as important benchmarks which are used to test the predictive power of new computational methods. By measuring many infrared transitions with precision at the sub-MHz level it is possible to construct a list of the most highly precise experimental rovibrational energy levels for this molecule. Until recently, only a select handful of infrared transitions of this molecule have been measured with high precision (˜ 1 MHz). Using the technique of Noise Immune Cavity Enhanced Optical Heterodyne Velocity Modulation Spectroscopy, we are aiming to produce the largest high-precision spectroscopic dataset for this molecule to date. Presented here are the current results from our survey along with a discussion of the combination differences analysis used to extract the experimentally determined rovibrational energy levels. O. Polyansky, et al., Phil. Trans. R. Soc. A (2012), 370, 5014. M. Pavanello, et al., J. Chem. Phys. (2012), 136, 184303. L. Diniz, et al., Phys. Rev. A (2013), 88, 032506. L. Lodi, et al., Phys. Rev. A (2014), 89, 032505. J. Hodges, et al., J. Chem. Phys (2013), 139, 164201.

Prebiotic chemical evolution in the astrophysical context.

PubMed

Ziurys, L M; Adande, G R; Edwards, J L; Schmidt, D R; Halfen, D T; Woolf, N J

2015-06-01

An ever increasing amount of molecular material is being discovered in the interstellar medium, associated with the birth and death of stars and planetary systems. Radio and millimeter-wave astronomical observations, made possible by high-resolution laboratory spectroscopy, uniquely trace the history of gas-phase molecules with biogenic elements. Using a combination of both disciplines, the full extent of the cycling of molecular matter, from circumstellar ejecta of dying stars - objects which expel large amounts of carbon - to nascent solar systems, has been investigated. Such stellar ejecta have been found to exhibit a rich and varied chemical content. Observations demonstrate that this molecular material is passed onto planetary nebulae, the final phase of stellar evolution. Here the star sheds almost its entire original mass, becoming an ultraviolet-emitting white dwarf. Molecules such as H2CO, HCN, HCO(+), and CCH are present in significant concentrations across the entire age span of such nebulae. These data suggest that gas-phase polyatomic, carbon-containing molecules survive the planetary nebula phase and subsequently are transported into the interstellar medium, seeding the chemistry of diffuse and then dense clouds. The extent of the chemical complexity in dense clouds is unknown, hindered by the high spectral line density. Organic species such as acetamide and methyl amine are present in such objects, and NH2CHO has a wide Galactic distribution. However, organophosphorus compounds have not yet been detected in dense clouds. Based on carbon and nitrogen isotope ratios, molecular material from the ISM appears to become incorporated into solar system planetesimals. It is therefore likely that interstellar synthesis influences prebiotic chemistry on planet surfaces.

Doppler Broadening Thermometry Based on Cavity Ring-Down Spectroscopy

NASA Astrophysics Data System (ADS)

Wang, Jin; Sun, Yu Robert; Cheng, Cunfeng; Tao, Lei-Gang; Tan, Yan; Kang, Peng; Liu, An-Wen; Hu, Shui-Ming

2016-06-01

A Doppler broadening thermometry (DBT) instrument is implemented based on a laser-locked cavity ring-down spectrometer. [1,2] It can be used to determine the Boltzmann constant by measuring the Doppler width of a molecular ro-vibrational transition in the near infrared. Compared with conventional direct absorption methods, the high-sensitivity of CRDS allows to reach satisfied precision at lower sample pressures, which reduces the influence due to collisions. By measuring the ro-vibrational transition of C_2H_2 at 787 nm, we demonstrate a statistical uncertainty of 6 ppm (part per million) in the determined linewidth by several hours' measurement at a sample pressure of 1.5 Pa. [3] However, the complicity in the spectrum of a polyatomic molecule induces potential systematic influence on the line profile due to nearby ``hidden'' lines from weak bands or minor isotopologues. Recently, the instrument has been upgraded in both sensitivity and frequency accuracy. A narrow-band fiber laser frequency-locked to a frequency comb is applied, and overtone transitions at 1.56 μm of the 12C16O molecule are used in the CRDS-DBT measurements. The simplicity of the spectrum of the diatomic CO molecule eliminates the potential influence from ``hidden'' lines. Our preliminary measurements and analysis show that it is feasible to pursue a DBT measurement toward the 1 ppm precision. H. Pan, et al., Rev. Sci. Instrum. 82, 103110 (2011) Y. R. Sun, et al., Opt. Expr., 19, 19993 (2011) C.-F. Cheng, et al., Metrologia, 52, S385 (2015)

The parity-adapted basis set in the formulation of the photofragment angular momentum polarization problem: The role of the Coriolis interaction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shternin, Peter S.; Vasyutinskii, Oleg S.

We present a theoretical framework for calculating the recoil-angle dependence of the photofragment angular momentum polarization taking into account both radial and Coriolis nonadiabatic interactions in the diatomic/linear photodissociating molecules. The parity-adapted representation of the total molecular wave function has been used throughout the paper. The obtained full quantum-mechanical expressions for the photofragment state multipoles have been simplified by using the semiclassical approximation in the high-J limit and then analyzed for the cases of direct photodissociation and slow predissociation in terms of the anisotropy parameters. In both cases, each anisotropy parameter can be presented as a linear combination of themore » generalized dynamical functions f{sub K}(q,q{sup '},q-tilde,q-tilde{sup '}) of the rank K representing contribution from different dissociation mechanisms including possible radial and Coriolis nonadiabatic transitions, coherent effects, and the rotation of the recoil axis. In the absence of the Coriolis interactions, the obtained results are equivalent to the earlier published ones. The angle-recoil dependence of the photofragment state multipoles for an arbitrary photolysis reaction is derived. As shown, the polarization of the photofragments in the photolysis of a diatomic or a polyatomic molecule can be described in terms of the anisotropy parameters irrespective of the photodissociation mechanism.« less

Photoelectron wave function in photoionization: plane wave or Coulomb wave?

PubMed

Gozem, Samer; Gunina, Anastasia O; Ichino, Takatoshi; Osborn, David L; Stanton, John F; Krylov, Anna I

2015-11-19

The calculation of absolute total cross sections requires accurate wave functions of the photoelectron and of the initial and final states of the system. The essential information contained in the latter two can be condensed into a Dyson orbital. We employ correlated Dyson orbitals and test approximate treatments of the photoelectron wave function, that is, plane and Coulomb waves, by comparing computed and experimental photoionization and photodetachment spectra. We find that in anions, a plane wave treatment of the photoelectron provides a good description of photodetachment spectra. For photoionization of neutral atoms or molecules with one heavy atom, the photoelectron wave function must be treated as a Coulomb wave to account for the interaction of the photoelectron with the +1 charge of the ionized core. For larger molecules, the best agreement with experiment is often achieved by using a Coulomb wave with a partial (effective) charge smaller than unity. This likely derives from the fact that the effective charge at the centroid of the Dyson orbital, which serves as the origin of the spherical wave expansion, is smaller than the total charge of a polyatomic cation. The results suggest that accurate molecular photoionization cross sections can be computed with a modified central potential model that accounts for the nonspherical charge distribution of the core by adjusting the charge in the center of the expansion.

New developments in theoretical thermochemistry and electronic structure applications in supramolecular chemistry and cluster science

NASA Astrophysics Data System (ADS)

Ramabhadran, Raghunath Ozhapakkam

In a concise display of the power and diversity of electronic structure theory (EST), the work presented herein involves the development of new computational methods to advance the practical utility of quantum chemistry, as well as solving different types of challenging chemical problems by applying existing EST tools. The research presented is highly interdisciplinary in nature and features synergistic collaborations to solve real-life problems such as regulating toxic chemicals and generating alternative sources of energy. In the first chapter of this dissertation, the solution to a long-standing problem in theoretical thermochemistry is accomplished by the development of the automated, chemically intuitive and generalized thermochemical hierarchy, Connectivity-Based Hierarchy (CBH) to accurately predict the thermochemical properties of organic molecules. The extension of the hierarchy to predict the enthalpies of formations of biomonomers such as amino acids is also presented. The development of a computationally efficient protocol to accurately extrapolate to high CCSD(T) energies based on MP2 and DFT energies using CBH is presented in the second chapter, thus merging theoretical thermochemistry with fragment-based methods in quantum chemistry. This merger drastically reduces the computational cost involved in a CCSD(T) calculation, while retaining the impeccable accuracy it offers. The practical utility of the CH hydrogen bond, commonly thought as being too weak to be used in supramolecular applications has been demonstrated by DFT calculations (along with experimental results from the Flood group) in the third chapter. This is accomplished by systematically studying the binding of monoatomic chloride, diatomic and toxic cyanide and the polyatomic bi-fluoride anions for the first time using only CH hydrogen bonds within a triazolophane macrocycle. The fourth chapter contains the introduction of the concept of fluxionality in the chemical reactions of transition metal oxide clusters. This is useful to develop a systematic paradigm for discussing the mechanisms in the reactions of larger transition metal oxide clusters with small molecules. Additionally, DFT calculations (along with experimental results from the C. C. Jarrold group) are shown to be useful to provide new insights on hydrogen liberation from water, thus aiding in the generation of alternative sources of energy.

Ab Initio Potential Energy Surfaces and Quantum Dynamics for Polyatomic Bimolecular Reactions.

PubMed

Fu, Bina; Zhang, Dong H

2018-05-08

There has been great progress in the development of potential energy surfaces (PESs) and quantum dynamics calculations in the gas phase. The establishment of a fitting procedure for highly accurate PESs and new developments in quantum reactive scattering on reliable PESs allow accurate characterization of reaction dynamics beyond triatomic systems. This review will give the recent development in our group in constructing ab initio PESs based on neural networks and the time-dependent wave packet calculations for bimolecular reactions beyond three atoms. Bimolecular reactions of current interest to the community, namely, OH + H 2 , H + H 2 O, OH + CO, H + CH 4 , and Cl + CH 4 , are focused on. Quantum mechanical characterization of these reactions uncovers interesting dynamical phenomena with an unprecedented level of sophistication and has greatly advanced our understanding of polyatomic reaction dynamics.

Molecular ion yield enhancement induced by gold deposition in static secondary ion mass spectrometry

NASA Astrophysics Data System (ADS)

Wehbe, Nimer; Delcorte, Arnaud; Heile, Andreas; Arlinghaus, Heinrich F.; Bertrand, Patrick

2008-12-01

Static ToF-SIMS was used to evaluate the effect of gold condensation as a sample treatment prior to analysis. The experiments were carried out with a model molecular layer (Triacontane M = 422.4 Da), upon atomic (In +) and polyatomic (Bi 3+) projectile bombardment. The results indicate that the effect of molecular ion yield improvement using gold metallization exists only under atomic projectile impact. While the quasi-molecular ion (M+Au) + signal can become two orders of magnitude larger than that of the deprotonated molecular ion from the pristine sample under In + bombardment, it barely reaches the initial intensity of (M-H) + when Bi 3+ projectiles are used. The differences observed for mono- and polyatomic primary ion bombardment might be explained by differences in near-surface energy deposition, which influences the sputtering and ionization processes.

A Separable Insertion Method to Calculate Atomic and Molecular Resonances on a FE-DVR Grid using Exterior Complex Scaling

NASA Astrophysics Data System (ADS)

Abeln, Brant Anthony

The study of metastable electronic resonances, anion or neutral states of finite lifetime, in molecules is an important area of research where currently no theoretical technique is generally applicable. The role of theory is to calculate both the position and width, which is proportional to the inverse of the lifetime, of these resonances and how they vary with respect to nuclear geometry in order to generate potential energy surfaces. These surfaces are the basis of time-dependent models of the molecular dynamics where the system moves towards vibrational excitation or fragmentation. Three fundamental electronic processes that can be modeled this way are dissociative electronic attachment, vibrational excitation through electronic impact and autoionization. Currently, experimental investigation into these processes is being preformed on polyatomic molecules while theoreticians continue their fifty-year-old search for robust methods to calculate them. The separable insertion method, investigated in this thesis, seeks to tackle the problem of calculating metastable resonances by using existing quantum chemistry tools along with a grid-based method employing exterior complex scaling (ECS). Modern quantum chemistry methods are extremely efficient at calculating ground and (bound) excited electronic states of atoms and molecules by utilizing Gaussian basis functions. These functions provide both a numerically fast and analytic solution to the necessary two-electron, six-dimensional integrals required in structure calculations. However, these computer programs, based on analytic Gaussian basis sets, cannot construct solutions that are not square-integrable, such as resonance wavefunctions. ECS, on the other hand, can formally calculate resonance solutions by rotating the asymptotic electronic coordinates into the complex plane. The complex Siegert energies for resonances, Eres = ER - iGamma/2 where ER is the real-valued position of the resonance and Gamma is the width of the resonance, can be found directly as an isolated pole in the complex energy plane. Unlike the straight complex scaling, ECS on the electronic coordinates overcomes the non-analytic behavior of the nuclear attraction potential, as a function of complex [special characters omitted] where the sum is over each nucleus in a molecular system. Discouragingly, the Gaussian basis functions, which are computationally well-suited for bound electronic structure, fail at forming an effective basis set for ECS due to the derivative discontinuity generated by the complex coordinate rotation and the piecewise defined contour. This thesis seeks to explore methods for implementing ECS indirectly without losing the numerical simplicity and power of Gaussian basis sets. The separable insertion method takes advantage of existing software by constructing a N2-term separable potential of the target system using Gaussian functions to be inserted into a finite-element discrete variable representation (FE-DVR) grid that implements ECS. This work reports an exhaustive investigation into this approach for calculating resonances. This thesis shows that this technique is successful at describing an anion shape resonance of a closed-shell atom or molecule in the static-exchange approximation. This method is applied to the 2P Be-, 2pig N2- and 2pi u CO2- shape resonances to calculate their complex Seigert energies. Additionally, many details on the exact construction of the separable potential and of the expansion basis are explored. The future work considers methods for faster convergence of the resonance energy, moving beyond the static-exchange approximation and applying this technique to polyatomic systems of interest.

Thermomagnetic torques in polyatomic gases

NASA Technical Reports Server (NTRS)

Hildebrandt, A. F.; Wood, C. T.

1972-01-01

The application of the Scott effect to the dynamics of galactic and stellar rotation is investigated. Efforts were also made to improve the sensitivity and stability of torque measurements and understand the microscopic mechanism that causes the Scott effect.

Peculiarities of high-overtone transition probabilities in carbon monoxide revealed by high-precision calculation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Medvedev, Emile S., E-mail: esmedved@orc.ru; Meshkov, Vladimir V.; Stolyarov, Andrey V.

In the recent work devoted to the calculation of the rovibrational line list of the CO molecule [G. Li et al., Astrophys. J., Suppl. Ser. 216, 15 (2015)], rigorous validation of the calculated parameters including intensities was carried out. In particular, the Normal Intensity Distribution Law (NIDL) [E. S. Medvedev, J. Chem. Phys. 137, 174307 (2012)] was employed for the validation purposes, and it was found that, in the original CO line list calculated for large changes of the vibrational quantum number up to Δn = 41, intensities with Δn > 11 were unphysical. Therefore, very high overtone transitions weremore » removed from the published list in Li et al. Here, we show how this type of validation is carried out and prove that the quadruple precision is indispensably required to predict the reliable intensities using the conventional 32-bit computers. Based on these calculations, the NIDL is shown to hold up for the 0 → n transitions till the dissociation limit around n = 83, covering 45 orders of magnitude in the intensity. The low-intensity 0 → n transition predicted in the work of Medvedev [Determination of a new molecular constant for diatomic systems. Normal intensity distribution law for overtone spectra of diatomic and polyatomic molecules and anomalies in overtone absorption spectra of diatomic molecules, Institute of Chemical Physics, Russian Academy of Sciences, Chernogolovka, 1984] at n = 5 is confirmed, and two additional “abnormal” intensities are found at n = 14 and 23. Criteria for the appearance of such “anomalies” are formulated. The results could be useful to revise the high-overtone molecular transition probabilities provided in spectroscopic databases.« less

Characteristics of energy exchange between inter- and intramolecular degrees of freedom in crystalline 1,3,5-triamino-2,4,6-trinitrobenzene (TATB) with implications for coarse-grained simulations of shock waves in polyatomic molecular crystals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kroonblawd, Matthew P.; Sewell, Thomas D., E-mail: sewellt@missouri.edu; Maillet, Jean-Bernard, E-mail: jean-bernard.maillet@cea.fr

2016-02-14

In this report, we characterize the kinetics and dynamics of energy exchange between intramolecular and intermolecular degrees of freedom (DoF) in crystalline 1,3,5-triamino-2,4,6-trinitrobenzene (TATB). All-atom molecular dynamics (MD) simulations are used to obtain predictions for relaxation from certain limiting initial distributions of energy between the intra- and intermolecular DoF. The results are used to parameterize a coarse-grained Dissipative Particle Dynamics at constant Energy (DPDE) model for TATB. Each TATB molecule in the DPDE model is represented as an all-atom, rigid-molecule mesoparticle, with explicit external (molecular translational and rotational) DoF and coarse-grained implicit internal (vibrational) DoF. In addition to conserving linearmore » and angular momentum, the DPDE equations of motion conserve the total system energy provided that particles can exchange energy between their external and internal DoF. The internal temperature of a TATB molecule is calculated using an internal equation of state, which we develop here, and the temperatures of the external and internal DoF are coupled using a fluctuation-dissipation relation. The DPDE force expression requires specification of the input parameter σ that determines the rate at which energy is exchanged between external and internal DoF. We adjusted σ based on the predictions for relaxation processes obtained from MD simulations. The parameterized DPDE model was employed in large-scale simulations of shock compression of TATB. We show that the rate of energy exchange governed by σ can significantly influence the transient behavior of the system behind the shock.« less

Characterising molecules for fundamental physics: an accurate spectroscopic model of methyltrioxorhenium derived from new infrared and millimetre-wave measurements.

PubMed

Asselin, Pierre; Berger, Yann; Huet, Thérèse R; Margulès, Laurent; Motiyenko, Roman; Hendricks, Richard J; Tarbutt, Michael R; Tokunaga, Sean K; Darquié, Benoît

2017-02-08

Precise spectroscopic analysis of polyatomic molecules enables many striking advances in physical chemistry and fundamental physics. We use several new high-resolution spectroscopic devices to improve our understanding of the rotational and rovibrational structure of methyltrioxorhenium (MTO), the achiral parent of a family of large oxorhenium compounds that are ideal candidate species for a planned measurement of parity violation in chiral molecules. Using millimetre-wave and infrared spectroscopy in a pulsed supersonic jet, a cryogenic buffer gas cell, and room temperature absorption cells, we probe the ground state and the Re[double bond, length as m-dash]O antisymmetric and symmetric stretching excited states of both CH 3 187 ReO 3 and CH 3 185 ReO 3 isotopologues in the gas phase with unprecedented precision. By extending the rotational spectra to the 150-300 GHz range, we characterize the ground state rotational and hyperfine structure up to J = 43 and K = 41, resulting in refinements to the rotational, quartic and hyperfine parameters, and the determination of sextic parameters and a centrifugal distortion correction to the quadrupolar hyperfine constant. We obtain rovibrational data for temperatures between 6 and 300 K in the 970-1015 cm -1 range, at resolutions down to 8 MHz and accuracies of 30 MHz. We use these data to determine more precise excited-state rotational, Coriolis and quartic parameters, as well as the ground-state centrifugal distortion parameter D K of the 187 Re isotopologue. We also account for hyperfine structure in the rovibrational transitions and hence determine the upper state rhenium atom quadrupole coupling constant eQq'.

Monoatomic and cluster beam effect on ToF-SIMS spectra of self-assembled monolayers on gold

NASA Astrophysics Data System (ADS)

Tuccitto, N.; Torrisi, V.; Delfanti, I.; Licciardello, A.

2008-12-01

Self-assembled monolayers represent well-defined systems that is a good model surface to study the effect of primary ion beams used in secondary ion mass spectrometry. The effect of polyatomic primary beams on both aliphatic and aromatic self-assembled monolayers has been studied. In particular, we analysed the variation of the relative secondary ion yield of both substrate metal-cluster (Au n-) in comparison with the molecular ions (M -) and clusters (M xAu y-) by using Bi +, Bi 3+, Bi 5+ beams. Moreover, the differences in the secondary ion generation efficiency are discussed. The main effect of the cluster beams is related to an increased formation of low-mass fragments and to the enhancement of the substrate related gold-clusters. The results show that, at variance of many other cases, the static SIMS of self-assembled monolayers does not benefit of the use of polyatomic primary ions.

Ab initio quantum direct dynamics simulations of ultrafast photochemistry with Multiconfigurational Ehrenfest approach

NASA Astrophysics Data System (ADS)

Makhov, Dmitry V.; Symonds, Christopher; Fernandez-Alberti, Sebastian; Shalashilin, Dmitrii V.

2017-08-01

The Multiconfigurational Ehrenfest (MCE) method is a quantum dynamics technique which allows treatment of a large number of quantum nuclear degrees of freedom. This paper presents a review of MCE and its recent applications, providing a summary of the formalisms, including its ab initio direct dynamics versions and also giving a summary of recent results. Firstly, we describe the Multiconfigurational Ehrenfest version 2 (MCEv2) method and its applicability to direct dynamics and report new calculations which show that the approach converges to the exact result in model systems with tens of degrees of freedom. Secondly, we review previous ;on the fly; ab initio Multiple Cloning (AIMC-MCE) MCE dynamics results obtained for systems of a similar size, in which the calculations treat every electron and every nucleus of a polyatomic molecule on a fully quantum basis. We also review the Time Dependent Diabatic Basis (TDDB) version of the technique and give an example of its application. We summarise the details of the sampling techniques and interpolations used for calculation of the matrix elements, which make our approach efficient. Future directions of work are outlined.

Physical explanation of the periodic table.

PubMed

Ostrovsky, V N

2003-05-01

The Periodic Table of the elements, the most important generalization in chemistry, is often considered as a representative special case in the study of the relation between chemistry and physics. Its quantum interpretation was initiated, but not completed, by Niels Bohr. In this paper, post-Bohr conceptual developments are discussed from historical and epistemological points of view. The difference between high-precision numerical calculations for individual atoms and the theory of the periodic system as a whole is emphasized. Periodic laws met in Nature are not restricted to the chemical Periodic Table. A comparative study of these laws makes it possible to single out essential features that define the particular pattern of periodicity. It is shown that the periodic system of neutral ground state atoms now has a firm nonempirical quantum-theoretical basis. Alternative approaches, based on group theory and other mathematical schemes, are briefly discussed. It is argued that, while quantum theory is capable of fully accurate calculations for relatively simple atoms or molecular objects, the complexity of polyatomic molecules and chemical reactions guarantees the flourishing of chemistry as a separate scientific discipline.

Picosecond coherent anti-Stokes Raman scattering (CARS) study of vibrational dephasing of carbon disulfide and benzene in solution

NASA Technical Reports Server (NTRS)

Perry, Joseph W.; Woodward, Anne M.; Stephenson, John C.

1986-01-01

The vibrational dephasing of the 656/cm mode (nu1, a1g) of CS2 and the 991/cm mode (nu2, a1g) of benzene have been studied as a function of concentration in mixtures with a number of solvents using a ps time-resolved CARS technique. This technique employs two tunable synchronously-pumped mode-locked dye lasers in a stimulated Raman pump, coherent anti-Stokes Raman probe time-resolved experiment. Results are obtained for CS2 in carbon tetrachloride, benzene, nitrobenzene, and ethanol and for benzene nu2 in CS2. The dephasing rates of CS2 nu1 increase on dilution with the polar solvents and decrease or remain constant on dilution with the nonpolar solvents. The CS2/benzene solutions show a contrasting behavior, with the CS2 nu1 dephasing rate being nearly independent of concentration whereas the benzene nu2 dephasing rate decreases on dilution. These results are compared to theoretical models for vibrational dephasing of polyatomic molecules in solution.

Hyperconjugation in the S1 State of Substituted Toluene Probed by Infrared Spectroscopy

NASA Astrophysics Data System (ADS)

Chiba, Takashi; Okuyama, Katsuhiko; Fujii, Asuka

2016-06-01

Internal rotation of the methyl group in substituted toluenes is one of prototypes of large amplitude motions in polyatomic molecules. The internal rotation of o-fluorotoluene is strongly hindered in the S0 state, but that of m-fluorotoluene is almost free. For the S1 state, however, the substantial changes of the internal rotation potentials have been reported; while the potential barrier in the o-isomer drastically decreases and the methyl group becomes almost a free rotor, the barrier in the m-isomer largely increases. These surprising barrier changes have been attributed to the methyl conformation-dependent stabilization in the S1 state by the π*-σ* hyperconjugation. In the present study, to test this interpretation, we observed infrared spectra of o- and m-fluorotoluenes in the S0 and S1 states. Both the isomers showed decrease of the methyl CH stretch frequencies upon the electronic excitation. We concluded that this frequency decrease is the evidence of the π*-σ* hyperconjugation. K,Okuyama.;N,Mikami.;M,Ito. J.Phys.Chem. 1985, 89, 5617 H,Nakai.;M,Kawai. Chem.Phys.Lett 1999, 307, 272

On the Mass of Atoms in Molecules: Beyond the Born-Oppenheimer Approximation

NASA Astrophysics Data System (ADS)

Scherrer, Arne; Agostini, Federica; Sebastiani, Daniel; Gross, E. K. U.; Vuilleumier, Rodolphe

2017-07-01

Describing the dynamics of nuclei in molecules requires a potential energy surface, which is traditionally provided by the Born-Oppenheimer or adiabatic approximation. However, we also need to assign masses to the nuclei. There, the Born-Oppenheimer picture does not account for the inertia of the electrons, and only bare nuclear masses are considered. Nowadays, experimental accuracy challenges the theoretical predictions of rotational and vibrational spectra and requires the participation of electrons in the internal motion of the molecule. More than 80 years after the original work of Born and Oppenheimer, this issue has still not been solved, in general. Here, we present a theoretical and numerical framework to address this problem in a general and rigorous way. Starting from the exact factorization of the electron-nuclear wave function, we include electronic effects beyond the Born-Oppenheimer regime in a perturbative way via position-dependent corrections to the bare nuclear masses. This maintains an adiabaticlike point of view: The nuclear degrees of freedom feel the presence of the electrons via a single potential energy surface, whereas the inertia of electrons is accounted for and the total mass of the system is recovered. This constitutes a general framework for describing the mass acquired by slow degrees of freedom due to the inertia of light, bounded particles; thus, it is applicable not only in electron-nuclear systems but in light-heavy nuclei or ions as well. We illustrate this idea with a model of proton transfer, where the light particle is the proton and the heavy particles are the oxygen atoms to which the proton is bounded. Inclusion of the light-particle inertia allows us to gain orders of magnitude in accuracy. The electron-nuclear perspective is adopted, instead, to calculate position-dependent mass corrections using density functional theory for a few polyatomic molecules at their equilibrium geometry. These data can serve as input for the computation of high-precision molecular spectra.

Molecular targets for small-molecule modulators of circadian clocks

PubMed Central

He, Baokun; Chen, Zheng

2016-01-01

Background Circadian clocks are endogenous timing systems that regulate various aspects of mammalian metabolism, physiology and behavior. Traditional chronotherapy refers to the administration of drugs in a defined circadian time window to achieve optimal pharmacokinetic and therapeutic efficacies. In recent years, substantial efforts have been dedicated to developing novel small-molecule modulators of circadian clocks. Methods Here, we review the recent progress in the identification of molecular targets of small-molecule clock modulators and their efficacies in clock-related disorders. Specifically, we examine the clock components and regulatory factors as possible molecular targets of small molecules, and we review several key clock-related disorders as promising venues for testing the preventive/therapeutic efficacies of these small molecules. Finally, we also discuss circadian regulation of drug metabolism. Results Small molecules can modulate the period, phase and/or amplitude of the circadian cycle. Core clock proteins, nuclear hormone receptors, and clock-related kinases and other epigenetic regulators are promising molecular targets for small molecules. Through these targets small molecules exert protective effects against clock-related disorders including the metabolic syndrome, immune disorders, sleep disorders and cancer. Small molecules can also modulate circadian drug metabolism and response to existing therapeutics. Conclusion Small-molecule clock modulators target clock components or diverse cellular pathways that functionally impinge upon the clock. Target identification of new small-molecule modulators will deepen our understanding of key regulatory nodes in the circadian network. Studies of clock modulators will facilitate their therapeutic applications, alone or in combination, for clock-related diseases. PMID:26750111

Recent advances in developing small molecules targeting RNA.

PubMed

Guan, Lirui; Disney, Matthew D

2012-01-20

RNAs are underexploited targets for small molecule drugs or chemical probes of function. This may be due, in part, to a fundamental lack of understanding of the types of small molecules that bind RNA specifically and the types of RNA motifs that specifically bind small molecules. In this review, we describe recent advances in the development and design of small molecules that bind to RNA and modulate function that aim to fill this void.

Mass Dependency of Isotope Fractionation of Gases Under Thermal Gradient and Its Possible Implications for Planetary Atmosphere Escaping Process

NASA Technical Reports Server (NTRS)

Sun, Tao; Niles, Paul; Bao, Huiming; Socki, Richard

2014-01-01

Physical processes that unmix elements/isotopes of gas molecules involve phase changes, diffusion (chemical or thermal), effusion and gravitational settling. Some of those play significant roles for the evolution of chemical and isotopic compositions of gases in planetary bodies which lead to better understanding of surface paleoclimatic conditions, e.g. gas bubbles in Antarctic ice, and planetary evolution, e.g. the solar-wind erosion induced gas escaping from exosphere on terrestrial planets.. A mass dependent relationship is always expected for the kinetic isotope fractionations during these simple physical processes, according to the kinetic theory of gases by Chapman, Enskog and others [3-5]. For O-bearing (O16, -O17, -O18) molecules the alpha O-17/ alpha O-18 is expected at 0.5 to 0.515, and for S-bearing (S32,-S33. -S34, -S36) molecules, the alpha S-33/ alpha S-34 is expected at 0.5 to 0.508, where alpha is the isotope fractionation factor associated with unmixing processes. Thus, one isotope pair is generally proxied to yield all the information for the physical history of the gases. However, we recently] reported the violation of mass law for isotope fractionation among isotope pairs of multiple isotope system during gas diffusion or convection under thermal gradient (Thermal Gradient Induced Non-Mass Dependent effect, TGI-NMD). The mechanism(s) that is responsible to such striking observation remains unanswered. In our past studies, we investigated polyatomic molecules, O2 and SF6, and we suggested that nuclear spin effect could be responsible to the observed NMD effect in a way of changing diffusion coefficients of certain molecules, owing to the fact of negligible delta S-36 anomaly for SF6.. On the other hand, our results also showed that for both diffusion and convection under thermal gradient, this NMD effect is increased by lower gas pressure, bigger temperature gradient and lower average temperature, which indicate that the nuclear spin effect may not be the significant contributor as the energies involved in the hyperfine effect are much smaller than those with molecular collisions, especially under convective conditions.

Line Shifts in Rotational Spectra of Polyatomic Chiral Molecules Caused by the Parity Violating Electroweak Interaction

NASA Astrophysics Data System (ADS)

Stohner, J.; Quack, M.

2009-06-01

Are findings in high-energy physics of any importance in molecular spectroscopy ? The answer is clearly `yes'. Energies of enantiomers were considered as exactly equal in an achiral environment, e.g. the gas phase. Today, however, it is well known that this is not valid. The violation of mirror-image symmetry (suggested theoretically and confirmed experimentally in 1956/57) was established in the field of nuclear, high-energy, and atomic physics since then, and it is also the cause for a non-zero energy difference between enantiomers. We expect today that the violation of mirror-image symmetry (parity violation) influences chemistry of chiral molecules as well as their spectroscopy. Progress has been made in the quantitative theoretical prediction of possible spectroscopic signatures of molecular parity violation. The experimental confirmation of parity violation in chiral molecules is, however, still open. Theoretical studies are helpful for the planning and important for a detailed analysis of rovibrational and tunneling spectra of chiral molecules. We report results on frequency shifts in rotational, vibrational and tunneling spectra of some selected chiral molecules which are studied in our group. If time permits, we shall also discuss critically some recent claims of experimental observations of molecular parity violation in condensed phase systems. T. D. Lee, C. N. Yang, Phys. Rev., 104, 254 (1956) C. S. Wu, E. Ambler, R. W. Hayward, D. D. Hoppes, R. P. Hudson, Phys. Rev., 105, 1413 (1957) M. Quack, Angew. Chem. Intl. Ed., 28, 571 (1989) Angew. Chem. Intl. Ed., 41, 4618 (2002) M. Quack, J. Stohner, Chimia, 59, 530 (2005) M. Quack, J. Stohner, M. Willeke, Ann Rev. Phys. Chem. 59, 741 (2008) M. Quack, J. Stohner, Phys. Rev. Lett., 84, 3807 (2000) M. Quack, J. Stohner, J. Chem. Phys., 119, 11228 (2003) J. Stohner, Int. J. Mass Spectrometry 233, 385 (2004) M. Gottselig, M. Quack, J. Stohner, M. Willeke, Int. J. Mass Spectrometry 233, 373 (2004) R. Berger, G. Laubender, M. Quack, A. Sieben, J. Stohner, M. Willeke, Angew. Chem. Intl. Ed., 44, 3623 (2005) J. Stohner, M. Quack, to be published

The Use of ICP-MS and IC-ICP-MS in Environmental and Exposure Assesssment

EPA Science Inventory

OVERVIEW: Application of collision/reaction cell interference reduction technology for the minimization of polyatomic interferences in environmental matrices. Improved risk assessments through the use of arsenic speciation approaches that estimate the bio-accessibility asso...

Rotating full- and reduced-dimensional quantum chemical models of molecules

NASA Astrophysics Data System (ADS)

Fábri, Csaba; Mátyus, Edit; Császár, Attila G.

2011-02-01

A flexible protocol, applicable to semirigid as well as floppy polyatomic systems, is developed for the variational solution of the rotational-vibrational Schrödinger equation. The kinetic energy operator is expressed in terms of curvilinear coordinates, describing the internal motion, and rotational coordinates, characterizing the orientation of the frame fixed to the nonrigid body. Although the analytic form of the kinetic energy operator might be very complex, it does not need to be known a priori within this scheme as it is constructed automatically and numerically whenever needed. The internal coordinates can be chosen to best represent the system of interest and the body-fixed frame is not restricted to an embedding defined with respect to a single reference geometry. The features of the technique mentioned make it especially well suited to treat large-amplitude nuclear motions. Reduced-dimensional rovibrational models can be defined straightforwardly by introducing constraints on the generalized coordinates. In order to demonstrate the flexibility of the protocol and the associated computer code, the inversion-tunneling of the ammonia (14NH3) molecule is studied using one, two, three, four, and six active vibrational degrees of freedom, within both vibrational and rovibrational variational computations. For example, the one-dimensional inversion-tunneling model of ammonia is considered also for nonzero rotational angular momenta. It turns out to be difficult to significantly improve upon this simple model. Rotational-vibrational energy levels are presented for rotational angular momentum quantum numbers J = 0, 1, 2, 3, and 4.

Photoelectron wave function in photoionization: Plane wave or Coulomb wave? [Does photoionization of neutral targets produce Coulomb or plane waves?

DOE PAGES

Gozem, Samer; Gunina, Anastasia O.; Ichino, Takatoshi; ...

2015-10-28

The calculation of absolute total cross sections requires accurate wave functions of the photoelectron and of the initial and final states of the system. The essential information contained in the latter two can be condensed into a Dyson orbital. We employ correlated Dyson orbitals and test approximate treatments of the photoelectron wave function, that is, plane and Coulomb waves, by comparing computed and experimental photoionization and photodetachment spectra. We find that in anions, a plane wave treatment of the photoelectron provides a good description of photodetachment spectra. For photoionization of neutral atoms or molecules with one heavy atom, the photoelectronmore » wave function must be treated as a Coulomb wave to account for the interaction of the photoelectron with the +1 charge of the ionized core. For larger molecules, the best agreement with experiment is often achieved by using a Coulomb wave with a partial (effective) charge smaller than unity. This likely derives from the fact that the effective charge at the centroid of the Dyson orbital, which serves as the origin of the spherical wave expansion, is smaller than the total charge of a polyatomic cation. Finally, the results suggest that accurate molecular photoionization cross sections can be computed with a modified central potential model that accounts for the nonspherical charge distribution of the core by adjusting the charge in the center of the expansion.« less

Molecular Abundances in the Disk of AN Active Galactic Nucleus

NASA Astrophysics Data System (ADS)

Harada, N.; Thompson, T. A.; Herbst, E.

2011-06-01

There are galactic nuclei that emit high luminosities L˜1044-46 erg S-1 including luminosity produced by X-rays from high mass accretion onto the central black holes. These nuclei are called active galactic nuclei (AGNs), and they are accompanied by molecular disks. Observations show high abundances of CN and HCN in the disks; the molecules are proposed to be probes of X-ray dominated regions (XDRs) created by the X-rays from AGNs. We have constructed a spatially-dependent chemical-abundance model of the molecular disk in NGC 1068, a typical AGN-dominated galaxy. Recently, new observations of CN and HCN have been made at much higher spatial resolution, and there are also detections of polyatomic molecules such as HC3N, c-C3H2, and C2H. We discuss how these observations and our simulations can help us to better understand the physical conditions, the disk structure, and conditions for star formation within molecular disks, which are still uncertain. We also include a comparison with other types of galaxies such as (ultra-) luminous infrared galaxies. Usero et al.Astronomy and Astrophysics. 419 (897), 2004. Initial results were presented at the International Symposium on Molecular Spectroscopy 2010, RF05 Garcia-Burillo et al. Astronomy and Astrophysics. 519 (2), 2010. Garcia-Burillo et al. Journal of Physics Conference Series, 131 (12031), 2008. Costagliola et al. ArXiv e-print arXiv:1101.2122, 2011. Nakajima et al. Astrophysical Journal Letters 728 (L38), 2008.

Following the Interstellar History of Carbon: From the Interiors of Stars to the Surfaces of Planets.

PubMed

Ziurys, L M; Halfen, D T; Geppert, W; Aikawa, Y

2016-12-01

The chemical history of carbon is traced from its origin in stellar nucleosynthesis to its delivery to planet surfaces. The molecular carriers of this element are examined at each stage in the cycling of interstellar organic material and their eventual incorporation into solar system bodies. The connection between the various interstellar carbon reservoirs is also examined. Carbon has two stellar sources: supernova explosions and mass loss from evolved stars. In the latter case, the carbon is dredged up from the interior and then ejected into a circumstellar envelope, where a rich and unusual C-based chemistry occurs. This molecular material is eventually released into the general interstellar medium through planetary nebulae. It is first incorporated into diffuse clouds, where carbon is found in polyatomic molecules such as H 2 CO, HCN, HNC, c-C 3 H 2 , and even C 60 + . These objects then collapse into dense clouds, the sites of star and planet formation. Such clouds foster an active organic chemistry, producing compounds with a wide range of functional groups with both gas-phase and surface mechanisms. As stars and planets form, the chemical composition is altered by increasing stellar radiation, as well as possibly by reactions in the presolar nebula. Some molecular, carbon-rich material remains pristine, however, encapsulated in comets, meteorites, and interplanetary dust particles, and is delivered to planet surfaces. Key Words: Carbon isotopes-Prebiotic evolution-Interstellar molecules-Comets-Meteorites. Astrobiology 16, 997-1012.

Interspecies scaling and prediction of human clearance: comparison of small- and macro-molecule drugs

PubMed Central

Huh, Yeamin; Smith, David E.; Feng, Meihau Rose

2014-01-01

Human clearance prediction for small- and macro-molecule drugs was evaluated and compared using various scaling methods and statistical analysis.Human clearance is generally well predicted using single or multiple species simple allometry for macro- and small-molecule drugs excreted renally.The prediction error is higher for hepatically eliminated small-molecules using single or multiple species simple allometry scaling, and it appears that the prediction error is mainly associated with drugs with low hepatic extraction ratio (Eh). The error in human clearance prediction for hepatically eliminated small-molecules was reduced using scaling methods with a correction of maximum life span (MLP) or brain weight (BRW).Human clearance of both small- and macro-molecule drugs is well predicted using the monkey liver blood flow method. Predictions using liver blood flow from other species did not work as well, especially for the small-molecule drugs. PMID:21892879

Using the QCM Biosensor-Based T7 Phage Display Combined with Bioinformatics Analysis for Target Identification of Bioactive Small Molecule.

PubMed

Takakusagi, Yoichi; Takakusagi, Kaori; Sugawara, Fumio; Sakaguchi, Kengo

2018-01-01

Identification of target proteins that directly bind to bioactive small molecule is of great interest in terms of clarifying the mode of action of the small molecule as well as elucidating the biological phenomena at the molecular level. Of the experimental technologies available, T7 phage display allows comprehensive screening of small molecule-recognizing amino acid sequence from the peptide libraries displayed on the T7 phage capsid. Here, we describe the T7 phage display strategy that is combined with quartz-crystal microbalance (QCM) biosensor for affinity selection platform and bioinformatics analysis for small molecule-recognizing short peptides. This method dramatically enhances efficacy and throughput of the screening for small molecule-recognizing amino acid sequences without repeated rounds of selection. Subsequent execution of bioinformatics programs allows combinatorial and comprehensive target protein discovery of small molecules with its binding site, regardless of protein sample insolubility, instability, or inaccessibility of the fixed small molecules to internally located binding site on larger target proteins when conventional proteomics approaches are used.

Bi-Directional Ion Emission from Massive Gold Cluster Impacts on Nanometric Carbon Foils.

PubMed

Debord, J Daniel; Della-Negra, Serge; Fernandez-Lima, Francisco A; Verkhoturov, Stanislav V; Schweikert, Emile A

2012-04-12

Carbon cluster emission from thin carbon foils (5-40 nm) impacted by individual Au(n) (+q) cluster projectiles (95-125 qkeV, n/q = 3-200) reveals features regarding the energy deposition, projectile range, and projectile fate in matter as a function of the projectile characteristics. For the first time, the secondary ion emission from thin foils has been monitored simultaneously in both forward and backward emission directions. The projectile range and depth of emission were examined as a function of projectile size, energy, and target thickness. A key finding is that the massive cluster impact develops very differently from that of a small polyatomic projectile. The range of the 125 qkeV Au(100q) (+q) (q ≈ 4) projectile is estimated to be 20 nm (well beyond the range of an equal velocity Au(+)) and projectile disintegration occurs at the exit of even a 5 nm thick foil.

Bi-Directional Ion Emission from Massive Gold Cluster Impacts on Nanometric Carbon Foils

PubMed Central

DeBord, J. Daniel; Della-Negra, Serge; Fernandez-Lima, Francisco A.; Verkhoturov, Stanislav V.; Schweikert, Emile A.

2012-01-01

Carbon cluster emission from thin carbon foils (5–40 nm) impacted by individual Aun+q cluster projectiles (95–125 qkeV, n/q = 3–200) reveals features regarding the energy deposition, projectile range, and projectile fate in matter as a function of the projectile characteristics. For the first time, the secondary ion emission from thin foils has been monitored simultaneously in both forward and backward emission directions. The projectile range and depth of emission were examined as a function of projectile size, energy, and target thickness. A key finding is that the massive cluster impact develops very differently from that of a small polyatomic projectile. The range of the 125 qkeV Au100q+q (q ≈ 4) projectile is estimated to be 20 nm (well beyond the range of an equal velocity Au+) and projectile disintegration occurs at the exit of even a 5 nm thick foil. PMID:22888385

Facilities for small-molecule crystallography at synchrotron sources.

PubMed

Barnett, Sarah A; Nowell, Harriott; Warren, Mark R; Wilcox, Andrian; Allan, David R

2016-01-01

Although macromolecular crystallography is a widely supported technique at synchrotron radiation facilities throughout the world, there are, in comparison, only very few beamlines dedicated to small-molecule crystallography. This limited provision is despite the increasing demand for beamtime from the chemical crystallography community and the ever greater overlap between systems that can be classed as either small macromolecules or large small molecules. In this article, a very brief overview of beamlines that support small-molecule single-crystal diffraction techniques will be given along with a more detailed description of beamline I19, a dedicated facility for small-molecule crystallography at Diamond Light Source.

Systems Based Study of the Therapeutic Potential of Small Charged Molecules for the Inhibition of IL-1 Mediated Cartilage Degradation

PubMed Central

Kar, Saptarshi; Smith, David W.; Gardiner, Bruce S.; Grodzinsky, Alan J.

2016-01-01

Inflammatory cytokines are key drivers of cartilage degradation in post-traumatic osteoarthritis. Cartilage degradation mediated by these inflammatory cytokines has been extensively investigated using in vitro experimental systems. Based on one such study, we have developed a computational model to quantitatively assess the impact of charged small molecules intended to inhibit IL-1 mediated cartilage degradation. We primarily focus on the simplest possible computational model of small molecular interaction with the IL-1 system—direct binding of the small molecule to the active site on the IL-1 molecule itself. We first use the model to explore the uptake and release kinetics of the small molecule inhibitor by cartilage tissue. Our results show that negatively charged small molecules are excluded from the negatively charged cartilage tissue and have uptake kinetics in the order of hours. In contrast, the positively charged small molecules are drawn into the cartilage with uptake and release timescales ranging from hours to days. Using our calibrated computational model, we subsequently explore the effect of small molecule charge and binding constant on the rate of cartilage degradation. The results from this analysis indicate that the small molecules are most effective in inhibiting cartilage degradation if they are either positively charged and/or bind strongly to IL-1α, or both. Furthermore, our results showed that the cartilage structural homeostasis can be restored by the small molecule if administered within six days following initial tissue exposure to IL-1α. We finally extended the scope of the computational model by simulating the competitive inhibition of cartilage degradation by the small molecule. Results from this model show that small molecules are more efficient in inhibiting cartilage degradation by binding directly to IL-1α rather than binding to IL-1α receptors. The results from this study can be used as a template for the design and development of more pharmacologically effective osteoarthritis drugs, and to investigate possible therapeutic options. PMID:27977731

Antibody-enabled small-molecule drug discovery.

PubMed

Lawson, Alastair D G

2012-06-29

Although antibody-based therapeutics have become firmly established as medicines for serious diseases, the value of antibodies as tools in the early stages of small-molecule drug discovery is only beginning to be realized. In particular, antibodies may provide information to reduce risk in small-molecule drug discovery by enabling the validation of targets and by providing insights into the design of small-molecule screening assays. Moreover, antibodies can act as guides in the quest for small molecules that have the ability to modulate protein-protein interactions, which have traditionally only been considered to be tractable targets for biological drugs. The development of small molecules that have similar therapeutic effects to current biologics has the potential to benefit a broader range of patients at earlier stages of disease.

Small Molecule Chemical Probes of MicroRNA Function

PubMed Central

Velagapudi, Sai Pradeep; Vummidi, Balayeshwanth R.; Disney, Matthew D.

2015-01-01

MicroRNAs (miRNAs) are small, non-coding RNAs that control protein expression. Aberrant miRNA expression has been linked to various human diseases, and thus miRNAs have been explored as diagnostic markers and therapeutic targets. Although it is challenging to target RNA with small molecules in general, there have been successful campaigns that have identified small molecule modulators of miRNA function by targeting various pathways. For example, small molecules that modulate transcription and target nuclease processing sites in miRNA precursors have been identified. Herein, we describe challenges in developing chemical probes that target miRNAs and highlight aspects of miRNA cellular biology elucidated by using small molecule chemical probes. We expect that this area will expand dramatically in the near future as strides are made to understand small molecule recognition of RNA from a fundamental perspective. PMID:25500006

Medium-Bandgap Small-Molecule Donors Compatible with Both Fullerene and Nonfullerene Acceptors.

PubMed

Huo, Yong; Yan, Cenqi; Kan, Bin; Liu, Xiao-Fei; Chen, Li-Chuan; Hu, Chen-Xia; Lau, Tsz-Ki; Lu, Xinhui; Sun, Chun-Lin; Shao, Xiangfeng; Chen, Yongsheng; Zhan, Xiaowei; Zhang, Hao-Li

2018-03-21

Much effort has been devoted to the development of new donor materials for small-molecule organic solar cells due to their inherent advantages of well-defined molecular weight, easy purification, and good reproducibility in photovoltaic performance. Herein, we report two small-molecule donors that are compatible with both fullerene and nonfullerene acceptors. Both molecules consist of an (E)-1,2-di(thiophen-2-yl)ethane-substituted (TVT-substituted) benzo[1,2-b:4,5-b']dithiophene (BDT) as the central unit, and two rhodanine units as the terminal electron-withdrawing groups. The central units are modified with either alkyl side chains (DRBDT-TVT) or alkylthio side chains (DRBDT-STVT). Both molecules exhibit a medium bandgap with complementary absorption and proper energy level offset with typical acceptors like PC 71 BM and IDIC. The optimized devices show a decent power conversion efficiency (PCE) of 6.87% for small-molecule organic solar cells and 6.63% for nonfullerene all small-molecule organic solar cells. Our results reveal that rationally designed medium-bandgap small-molecule donors can be applied in high-performance small-molecule organic solar cells with different types of acceptors.

Inforna 2.0: A Platform for the Sequence-Based Design of Small Molecules Targeting Structured RNAs.

PubMed

Disney, Matthew D; Winkelsas, Audrey M; Velagapudi, Sai Pradeep; Southern, Mark; Fallahi, Mohammad; Childs-Disney, Jessica L

2016-06-17

The development of small molecules that target RNA is challenging yet, if successful, could advance the development of chemical probes to study RNA function or precision therapeutics to treat RNA-mediated disease. Previously, we described Inforna, an approach that can mine motifs (secondary structures) within target RNAs, which is deduced from the RNA sequence, and compare them to a database of known RNA motif-small molecule binding partners. Output generated by Inforna includes the motif found in both the database and the desired RNA target, lead small molecules for that target, and other related meta-data. Lead small molecules can then be tested for binding and affecting cellular (dys)function. Herein, we describe Inforna 2.0, which incorporates all known RNA motif-small molecule binding partners reported in the scientific literature, a chemical similarity searching feature, and an improved user interface and is freely available via an online web server. By incorporation of interactions identified by other laboratories, the database has been doubled, containing 1936 RNA motif-small molecule interactions, including 244 unique small molecules and 1331 motifs. Interestingly, chemotype analysis of the compounds that bind RNA in the database reveals features in small molecule chemotypes that are privileged for binding. Further, this updated database expanded the number of cellular RNAs to which lead compounds can be identified.

Mapping the Small Molecule Interactome by Mass Spectrometry.

PubMed

Flaxman, Hope A; Woo, Christina M

2018-01-16

Mapping small molecule interactions throughout the proteome provides the critical structural basis for functional analysis of their impact on biochemistry. However, translation of mass spectrometry-based proteomics methods to directly profile the interaction between a small molecule and the whole proteome is challenging because of the substoichiometric nature of many interactions, the diversity of covalent and noncovalent interactions involved, and the subsequent computational complexity associated with their spectral assignment. Recent advances in chemical proteomics have begun fill this gap to provide a structural basis for the breadth of small molecule-protein interactions in the whole proteome. Innovations enabling direct characterization of the small molecule interactome include faster, more sensitive instrumentation coupled to chemical conjugation, enrichment, and labeling methods that facilitate detection and assignment. These methods have started to measure molecular interaction hotspots due to inherent differences in local amino acid reactivity and binding affinity throughout the proteome. Measurement of the small molecule interactome is producing structural insights and methods for probing and engineering protein biochemistry. Direct structural characterization of the small molecule interactome is a rapidly emerging area pushing new frontiers in biochemistry at the interface of small molecules and the proteome.

Analysis of seven salad rocket (Eruca sativa) accessions: The relationships between sensory attributes and volatile and non-volatile compounds.

PubMed

Bell, Luke; Methven, Lisa; Signore, Angelo; Oruna-Concha, Maria Jose; Wagstaff, Carol

2017-03-01

Sensory and chemical analyses were performed on accessions of rocket (Eruca sativa) to determine phytochemical influences on sensory attributes. A trained panel was used to evaluate leaves, and chemical data were obtained for polyatomic ions, amino acids, sugars and organic acids. These chemical data (and data of glucosinolates, flavonols and headspace volatiles previously reported) were used in Principal Component Analysis (PCA) to determine variables statistically important to sensory traits. Significant differences were observed between samples for polyatomic ion and amino acid concentrations. PCA revealed strong, positive correlations between glucosinolates, isothiocyanates and sulfur compounds with bitterness, mustard, peppery, warming and initial heat mouthfeel traits. The ratio between glucosinolates and sugars inferred reduced perception of bitter aftereffects. We highlight the diversity of E. sativa accessions from a sensory and phytochemical standpoint, and the potential for breeders to create varieties that are nutritionally and sensorially superior to existing ones. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Small molecule chemical probes of microRNA function.

PubMed

Velagapudi, Sai Pradeep; Vummidi, Balayeshwanth R; Disney, Matthew D

2015-02-01

MicroRNAs (miRNAs) are small, non-coding RNAs that control protein expression. Aberrant miRNA expression has been linked to various human diseases, and thus miRNAs have been explored as diagnostic markers and therapeutic targets. Although it is challenging to target RNA with small molecules in general, there have been successful campaigns that have identified small molecule modulators of miRNA function by targeting various pathways. For example, small molecules that modulate transcription and target nuclease processing sites in miRNA precursors have been identified. Herein, we describe challenges in developing chemical probes that target miRNAs and highlight aspects of miRNA cellular biology elucidated by using small molecule chemical probes. We expect that this area will expand dramatically in the near future as progress is made in understanding small molecule recognition of RNA. Copyright © 2014. Published by Elsevier Ltd.

Defining RNA-Small Molecule Affinity Landscapes Enables Design of a Small Molecule Inhibitor of an Oncogenic Noncoding RNA.

PubMed

Velagapudi, Sai Pradeep; Luo, Yiling; Tran, Tuan; Haniff, Hafeez S; Nakai, Yoshio; Fallahi, Mohammad; Martinez, Gustavo J; Childs-Disney, Jessica L; Disney, Matthew D

2017-03-22

RNA drug targets are pervasive in cells, but methods to design small molecules that target them are sparse. Herein, we report a general approach to score the affinity and selectivity of RNA motif-small molecule interactions identified via selection. Named High Throughput Structure-Activity Relationships Through Sequencing (HiT-StARTS), HiT-StARTS is statistical in nature and compares input nucleic acid sequences to selected library members that bind a ligand via high throughput sequencing. The approach allowed facile definition of the fitness landscape of hundreds of thousands of RNA motif-small molecule binding partners. These results were mined against folded RNAs in the human transcriptome and identified an avid interaction between a small molecule and the Dicer nuclease-processing site in the oncogenic microRNA (miR)-18a hairpin precursor, which is a member of the miR-17-92 cluster. Application of the small molecule, Targapremir-18a, to prostate cancer cells inhibited production of miR-18a from the cluster, de-repressed serine/threonine protein kinase 4 protein (STK4), and triggered apoptosis. Profiling the cellular targets of Targapremir-18a via Chemical Cross-Linking and Isolation by Pull Down (Chem-CLIP), a covalent small molecule-RNA cellular profiling approach, and other studies showed specific binding of the compound to the miR-18a precursor, revealing broadly applicable factors that govern small molecule drugging of noncoding RNAs.

Energy partitioning in polyatomic chemical reactions: Quantum state resolved studies of highly exothermic atom abstraction reactions from molecules in the gas phase and at the gas-liquid interface

NASA Astrophysics Data System (ADS)

Zolot, Alexander M.

This thesis recounts a series of experiments that interrogate the dynamics of elementary chemical reactions using quantum state resolved measurements of gas-phase products. The gas-phase reactions F + HCl → HF + Cl and F + H2O → HF + OH are studied using crossed supersonic jets under single collision conditions. Infrared (IR) laser absorption probes HF product with near shot-noise limited sensitivity and high resolution, capable of resolving rovibrational states and Doppler lineshapes. Both reactions yield inverted vibrational populations. For the HCl reaction, strongly bimodal rotational distributions are observed, suggesting microscopic branching of the reaction mechanism. Alternatively, such structure may result from a quantum-resonance mediated reaction similar to those found in the well-characterized F + HD system. For the H2O reaction, a small, but significant, branching into v = 2 is particularly remarkable because this manifold is accessible only via the additional center of mass collision energy in the crossed jets. Rotationally hyperthermal HF is also observed. Ab initio calculations of the transition state geometry suggest mechanisms for both rotational and vibrational excitation. Exothermic chemical reaction dynamics at the gas-liquid interface have been investigated by colliding a supersonic jet of F atoms with liquid squalane (C30H62), a low vapor pressure hydrocarbon compatible with the high vacuum environment. IR spectroscopy provides absolute HF( v,J) product densities and Doppler resolved velocity component distributions perpendicular to the surface normal. Compared to analogous gas-phase F + hydrocarbon reactions, the liquid surface is a more effective "heat sink," yet vibrationally excited populations reveal incomplete thermal accommodation with the surface. Non-Boltzmann J-state populations and hot Doppler lineshapes that broaden with HF excitation indicate two competing scattering mechanisms: (i) a direct reactive scattering channel, whereby newly formed molecules leave the surface without equilibrating, and (ii) a partially accommodated fraction that shares vibrational, rotational, and translational energy with the liquid surface before returning to the gas phase. Finally, a velocity map ion imaging apparatus has been implemented to investigate reaction dynamics in crossed molecular beams. Resonantly enhanced multiphoton ionization (REMPI) results in rotational, vibrational, and electronic state selectivity. Velocity map imaging measurements provide differential cross sections and information about the internal energy distribution of the undetected collision partner.

Small Molecule Inhibitors of AI-2 Signaling in Bacteria: State-of-the-Art and Future Perspectives for Anti-Quorum Sensing Agents

PubMed Central

Guo, Min; Gamby, Sonja; Zheng, Yue; Sintim, Herman O.

2013-01-01

Bacteria respond to different small molecules that are produced by other neighboring bacteria. These molecules, called autoinducers, are classified as intraspecies (i.e., molecules produced and perceived by the same bacterial species) or interspecies (molecules that are produced and sensed between different bacterial species). AI-2 has been proposed as an interspecies autoinducer and has been shown to regulate different bacterial physiology as well as affect virulence factor production and biofilm formation in some bacteria, including bacteria of clinical relevance. Several groups have embarked on the development of small molecules that could be used to perturb AI-2 signaling in bacteria, with the ultimate goal that these molecules could be used to inhibit bacterial virulence and biofilm formation. Additionally, these molecules have the potential to be used in synthetic biology applications whereby these small molecules are used as inputs to switch on and off AI-2 receptors. In this review, we highlight the state-of-the-art in the development of small molecules that perturb AI-2 signaling in bacteria and offer our perspective on the future development and applications of these classes of molecules. PMID:23994835

Organic small molecule semiconducting chromophores for use in organic electronic devices

DOE Office of Scientific and Technical Information (OSTI.GOV)

Welch, Gregory C.; Hoven, Corey V.; Nguyen, Thuc-Quyen

Small organic molecule semi-conducting chromophores containing a pyridalthiadiazole, pyridaloxadiazole, or pyridaltriazole core structure are disclosed. Such compounds can be used in organic heterojunction devices, such as organic small molecule solar cells and transistors.

Structure-guided Discovery of Dual-recognition Chemibodies.

PubMed

Cheng, Alan C; Doherty, Elizabeth M; Johnstone, Sheree; DiMauro, Erin F; Dao, Jennifer; Luthra, Abhinav; Ye, Jay; Tang, Jie; Nixey, Thomas; Min, Xiaoshan; Tagari, Philip; Miranda, Les P; Wang, Zhulun

2018-05-15

Small molecules and antibodies each have advantages and limitations as therapeutics. Here, we present for the first time to our knowledge, the structure-guided design of "chemibodies" as small molecule-antibody hybrids that offer dual recognition of a single target by both a small molecule and an antibody, using DPP-IV enzyme as a proof of concept study. Biochemical characterization demonstrates that the chemibodies present superior DPP-IV inhibition compared to either small molecule or antibody component alone. We validated our design by successfully solving a co-crystal structure of a chemibody in complex with DPP-IV, confirming specific binding of the small molecule portion at the interior catalytic site and the Fab portion at the protein surface. The discovery of chemibodies presents considerable potential for novel therapeutics that harness the power of both small molecule and antibody modalities to achieve superior specificity, potency, and pharmacokinetic properties.

Rational design of chemical genetic probes of RNA function and lead therapeutics targeting repeating transcripts.

PubMed

Disney, Matthew D

2013-12-01

RNA is an important yet vastly underexploited target for small molecule chemical probes or lead therapeutics. Small molecules have been used successfully to modulate the function of the bacterial ribosome, viral RNAs and riboswitches. These RNAs are either highly expressed or can be targeted using substrate mimicry, a mainstay in the design of enzyme inhibitors. However, most cellular RNAs are neither highly expressed nor have a lead small molecule inhibitor, a significant challenge for drug discovery efforts. Herein, I describe the design of small molecules targeting expanded repeating transcripts that cause myotonic muscular dystrophy (DM). These test cases illustrate the challenges of designing small molecules that target RNA and the advantages of targeting repeating transcripts. Lastly, I discuss how small molecules might be more advantageous than oligonucleotides for targeting RNA. Copyright © 2013 Elsevier Ltd. All rights reserved.

Advancing Biological Understanding and Therapeutics Discovery with Small Molecule Probes

PubMed Central

Schreiber, Stuart L.; Kotz, Joanne D.; Li, Min; Aubé, Jeffrey; Austin, Christopher P.; Reed, John C.; Rosen, Hugh; White, E. Lucile; Sklar, Larry A.; Lindsley, Craig W.; Alexander, Benjamin R.; Bittker, Joshua A.; Clemons, Paul A.; de Souza, Andrea; Foley, Michael A.; Palmer, Michelle; Shamji, Alykhan F.; Wawer, Mathias J.; McManus, Owen; Wu, Meng; Zou, Beiyan; Yu, Haibo; Golden, Jennifer E.; Schoenen, Frank J.; Simeonov, Anton; Jadhav, Ajit; Jackson, Michael R.; Pinkerton, Anthony B.; Chung, Thomas D.Y.; Griffin, Patrick R.; Cravatt, Benjamin F.; Hodder, Peter S.; Roush, William R.; Roberts, Edward; Chung, Dong-Hoon; Jonsson, Colleen B.; Noah, James W.; Severson, William E.; Ananthan, Subramaniam; Edwards, Bruce; Oprea, Tudor I.; Conn, P. Jeffrey; Hopkins, Corey R.; Wood, Michael R.; Stauffer, Shaun R.; Emmitte, Kyle A.

2015-01-01

Small-molecule probes can illuminate biological processes and aid in the assessment of emerging therapeutic targets by perturbing biological systems in a manner distinct from other experimental approaches. Despite the tremendous promise of chemical tools for investigating biology and disease, small-molecule probes were unavailable for most targets and pathways as recently as a decade ago. In 2005, the U.S. National Institutes of Health launched the decade-long Molecular Libraries Program with the intent of innovating in and broadening access to small-molecule science. This Perspective describes how novel small-molecule probes identified through the program are enabling the exploration of biological pathways and therapeutic hypotheses not otherwise testable. These experiences illustrate how small-molecule probes can help bridge the chasm between biological research and the development of medicines, but also highlight the need to innovate the science of therapeutic discovery. PMID:26046436

High mobility high efficiency organic films based on pure organic materials

DOEpatents

Salzman, Rhonda F [Ann Arbor, MI; Forrest, Stephen R [Ann Arbor, MI

2009-01-27

A method of purifying small molecule organic material, performed as a series of operations beginning with a first sample of the organic small molecule material. The first step is to purify the organic small molecule material by thermal gradient sublimation. The second step is to test the purity of at least one sample from the purified organic small molecule material by spectroscopy. The third step is to repeat the first through third steps on the purified small molecule material if the spectroscopic testing reveals any peaks exceeding a threshold percentage of a magnitude of a characteristic peak of a target organic small molecule. The steps are performed at least twice. The threshold percentage is at most 10%. Preferably the threshold percentage is 5% and more preferably 2%. The threshold percentage may be selected based on the spectra of past samples that achieved target performance characteristics in finished devices.

One-dimensional cuts through multidimensional potential-energy surfaces by tunable x rays

NASA Astrophysics Data System (ADS)

Eckert, Sebastian; da Cruz, Vinícius Vaz; Gel'mukhanov, Faris; Ertan, Emelie; Ignatova, Nina; Polyutov, Sergey; Couto, Rafael C.; Fondell, Mattis; Dantz, Marcus; Kennedy, Brian; Schmitt, Thorsten; Pietzsch, Annette; Odelius, Michael; Föhlisch, Alexander

2018-05-01

The concept of the potential-energy surface (PES) and directional reaction coordinates is the backbone of our description of chemical reaction mechanisms. Although the eigenenergies of the nuclear Hamiltonian uniquely link a PES to its spectrum, this information is in general experimentally inaccessible in large polyatomic systems. This is due to (near) degenerate rovibrational levels across the parameter space of all degrees of freedom, which effectively forms a pseudospectrum given by the centers of gravity of groups of close-lying vibrational levels. We show here that resonant inelastic x-ray scattering (RIXS) constitutes an ideal probe for revealing one-dimensional cuts through the ground-state PES of molecular systems, even far away from the equilibrium geometry, where the independent-mode picture is broken. We strictly link the center of gravity of close-lying vibrational peaks in RIXS to a pseudospectrum which is shown to coincide with the eigenvalues of an effective one-dimensional Hamiltonian along the propagation coordinate of the core-excited wave packet. This concept, combined with directional and site selectivity of the core-excited states, allows us to experimentally extract cuts through the ground-state PES along three complementary directions for the showcase H2O molecule.

Approximate Quantum Dynamics using Ab Initio Classical Separable Potentials: Spectroscopic Applications.

PubMed

Hirshberg, Barak; Sagiv, Lior; Gerber, R Benny

2017-03-14

Algorithms for quantum molecular dynamics simulations that directly use ab initio methods have many potential applications. In this article, the ab initio classical separable potentials (AICSP) method is proposed as the basis for approximate algorithms of this type. The AICSP method assumes separability of the total time-dependent wave function of the nuclei and employs mean-field potentials that govern the dynamics of each degree of freedom. In the proposed approach, the mean-field potentials are determined by classical ab initio molecular dynamics simulations. The nuclear wave function can thus be propagated in time using the effective potentials generated "on the fly". As a test of the method for realistic systems, calculations of the stationary anharmonic frequencies of hydrogen stretching modes were carried out for several polyatomic systems, including three amino acids and the guanine-cytosine pair of nucleobases. Good agreement with experiments was found. The method scales very favorably with the number of vibrational modes and should be applicable for very large molecules, e.g., peptides. The method should also be applicable for properties such as vibrational line widths and line shapes. Work in these directions is underway.

Native Frames: Disentangling Sequential from Concerted Three-Body Fragmentation

NASA Astrophysics Data System (ADS)

Rajput, Jyoti; Severt, T.; Berry, Ben; Jochim, Bethany; Feizollah, Peyman; Kaderiya, Balram; Zohrabi, M.; Ablikim, U.; Ziaee, Farzaneh; Raju P., Kanaka; Rolles, D.; Rudenko, A.; Carnes, K. D.; Esry, B. D.; Ben-Itzhak, I.

2018-03-01

A key question concerning the three-body fragmentation of polyatomic molecules is the distinction of sequential and concerted mechanisms, i.e., the stepwise or simultaneous cleavage of bonds. Using laser-driven fragmentation of OCS into O++C++S+ and employing coincidence momentum imaging, we demonstrate a novel method that enables the clear separation of sequential and concerted breakup. The separation is accomplished by analyzing the three-body fragmentation in the native frame associated with each step and taking advantage of the rotation of the intermediate molecular fragment, CO2 + or CS2 + , before its unimolecular dissociation. This native-frame method works for any projectile (electrons, ions, or photons), provides details on each step of the sequential breakup, and enables the retrieval of the relevant spectra for sequential and concerted breakup separately. Specifically, this allows the determination of the branching ratio of all these processes in OCS3 + breakup. Moreover, we find that the first step of sequential breakup is tightly aligned along the laser polarization and identify the likely electronic states of the intermediate dication that undergo unimolecular dissociation in the second step. Finally, the separated concerted breakup spectra show clearly that the central carbon atom is preferentially ejected perpendicular to the laser field.

Sudoku Puzzles as Chemistry Learning Tools

ERIC Educational Resources Information Center

Crute, Thomas D.; Myers, Stephanie A.

2007-01-01

A sudoku puzzle was designed that incorporated lists of chemistry terms like polyatomic ions, organic functional groups or strong nucleophiles that students need to learn. It was found that students enjoyed solving such puzzles and also such puzzles made the boring tasks of memorizing basic chemical terms an exciting one.

Characterizing protein domain associations by Small-molecule ligand binding

PubMed Central

Li, Qingliang; Cheng, Tiejun; Wang, Yanli; Bryant, Stephen H.

2012-01-01

Background Protein domains are evolutionarily conserved building blocks for protein structure and function, which are conventionally identified based on protein sequence or structure similarity. Small molecule binding domains are of great importance for the recognition of small molecules in biological systems and drug development. Many small molecules, including drugs, have been increasingly identified to bind to multiple targets, leading to promiscuous interactions with protein domains. Thus, a large scale characterization of the protein domains and their associations with respect to small-molecule binding is of particular interest to system biology research, drug target identification, as well as drug repurposing. Methods We compiled a collection of 13,822 physical interactions of small molecules and protein domains derived from the Protein Data Bank (PDB) structures. Based on the chemical similarity of these small molecules, we characterized pairwise associations of the protein domains and further investigated their global associations from a network point of view. Results We found that protein domains, despite lack of similarity in sequence and structure, were comprehensively associated through binding the same or similar small-molecule ligands. Moreover, we identified modules in the domain network that consisted of closely related protein domains by sharing similar biochemical mechanisms, being involved in relevant biological pathways, or being regulated by the same cognate cofactors. Conclusions A novel protein domain relationship was identified in the context of small-molecule binding, which is complementary to those identified by traditional sequence-based or structure-based approaches. The protein domain network constructed in the present study provides a novel perspective for chemogenomic study and network pharmacology, as well as target identification for drug repurposing. PMID:23745168

Proteoform-specific protein binding of small molecules in complex matrices

USDA-ARS?s Scientific Manuscript database

Characterizing the specific binding between protein targets and small molecules is critically important for drug discovery. Conventional assays require isolation and purification of small molecules from complex matrices through multistep chromatographic fractionation, which may alter their original ...

Full-dimensional treatment of short-time vibronic dynamics in a molecular high-order-harmonic-generation process in methane

NASA Astrophysics Data System (ADS)

Patchkovskii, Serguei; Schuurman, Michael S.

2017-11-01

We present derivation and implementation of the multiconfigurational strong-field approximation with Gaussian nuclear wave packets (MC-SFA-GWP)—a version of the molecular strong-field approximation which treats all electronic and nuclear degrees of freedom, including their correlations, quantum mechanically. The technique allows realistic simulation of high-order-harmonic emission in polyatomic molecules without invoking reduced-dimensionality models for the nuclear motion or the electronic structure. We use MC-SFA-GWP to model isotope effects in high-order-harmonic-generation (HHG) spectroscopy of methane. The HHG emission in this molecule transiently involves the strongly vibronically coupled F22 electronic state of the CH4+ cation. We show that the isotopic HHG ratio in methane contains signatures of (a) field-free vibronic dynamics at the conical intersection (CI); (b) resonant features in the recombination cross sections; (c) laser-driven bound-state dynamics; as well as (d) the well-known short-time Gaussian decay of the emission. We assign the intrinsic vibronic feature (a) to a relatively long-lived (≥4 fs) vibronic wave packet of the singly excited ν4 (t2) and ν2 (e ) vibrational modes, strongly coupled to the components of the F22 electronic state. We demonstrate that these physical effects differ in their dependence on the wavelength, intensity, and duration of the driving pulse, allowing them to be disentangled. We thus show that HHG spectroscopy provides a versatile tool for exploring both conical intersections and resonant features in photorecombination matrix elements in the regime not easily accessible with other techniques.

Quantum Theories of Self-Localization

NASA Astrophysics Data System (ADS)

Bernstein, Lisa Joan

In the classical dynamics of coupled oscillator systems, nonlinearity leads to the existence of stable solutions in which energy remains localized for all time. Here the quantum-mechanical counterpart of classical self-localization is investigated in the context of two model systems. For these quantum models, the terms corresponding to classical nonlinearities modify a subset of the stationary quantum states to be particularly suited to the creation of nonstationary wavepackets that localize energy for long times. The first model considered here is the Quantized Discrete Self-Trapping model (QDST), a system of anharmonic oscillators with linear dispersive coupling used to model local modes of vibration in polyatomic molecules. A simple formula is derived for a particular symmetry class of QDST systems which gives an analytic connection between quantum self-localization and classical local modes. This formula is also shown to be useful in the interpretation of the vibrational spectra of some molecules. The second model studied is the Frohlich/Einstein Dimer (FED), a two-site system of anharmonically coupled oscillators based on the Frohlich Hamiltonian and motivated by the theory of Davydov solitons in biological protein. The Born-Oppenheimer perturbation method is used to obtain approximate stationary state wavefunctions with error estimates for the FED at the first excited level. A second approach is used to reduce the first excited level FED eigenvalue problem to a system of ordinary differential equations. A simple theory of low-energy self-localization in the FED is discussed. The quantum theories of self-localization in the intrinsic QDST model and the extrinsic FED model are compared.

Stereodynamics of the reactions: F + H2/HD/HT→FH + H/D/T

NASA Astrophysics Data System (ADS)

Chi, Xiao-Lin; Zhao, Jin-Feng; Zhang, Yong-Jia; Ma, Feng-Cai; Li, Yong-Qing

2015-05-01

Among many kinds of ways to study the properties of atom and molecule collision, the quasi-classical trajectory (QCT) method is an effective one to investigate the molecular reaction dynamics. QCT calculations have been carried out to investigate the stereodynamics of the reactions F + H2/HD/HT→FH + H/D/T, which proceed on the lowest-lying electronic states of the FH2 system based on the potential energy surface (PES) of the 12A’ FH2 ground state. Although the QCT method cannot describe all quantum effects in the process of the reaction, it has unique advantages when facing a three-atoms system or complicated polyatomic systems. Differential cross sections (DCSs) and three angle distribution functions P(θr), P(ϕr), P(θr, ϕr) on the PES at the collision of 2.74 kcal/mol have been investigated. The isotope effect becomes more obvious with the reagent molecule H2 turning into HD and HT. P(θr, ϕr), as the joint probability density function of both polar angles θr and ϕr, can reflect the properties of three-dimensional dynamic more intuitively. Project supported by the National Natural Science Foundation of China (Grant No. 11474141), the Scientific Research Foundation for the Returned Overseas Chinese Scholars (Grant No. 2014-1685), the Scientific Research Foundation for the Doctor of Liaoning University, the Special Fund Based Research New Technology of Methanol Conversion and Coal Instead of Oil, and the China Postdoctoral Science Foundation (Grant No. 2014M550158).

Rotational and vibrotational transfer in H*-CO2 collisions: The influence of stereokinematic restrictions

NASA Astrophysics Data System (ADS)

Clare, Suzanne; Marks, Alison J.; McCaffery, Anthony J.

1999-11-01

We describe a quantitative angular momentum (AM) model for predicting rotational transfer (RT) and vibrotational transfer (VRT) in collisions between CO2 and hot H atoms. This molecule is important in several contexts, not least as a bridge between the relative simplicity of diatomic molecules and the complexities of polyatomic RT and VRT. We show that for pure RT, an AM constraint dominates but that this changes to a dominant energetic constraint in the case of VRT. The requirement that the (001) vibrational channel be opened simultaneously with the generation of AM imposes special restrictions which effectively limit the trajectories that lead to VRT. The origin of this is a constraint-induced restriction on the effective impact parameter (bnmax) for individual Δj channels and the effect is manifest as reduced probability for populating low Δj channels. In CO2-H* this leads to a shift in the peak of (VRT) Δj probabilities away from zero as found experimentally for the (001) vibrational mode. We report a Monte Carlo trajectory calculation similar to that of Kreutz and Flynn [J. Chem. Phys. 93, 452 (1990)] but predict an exponential-like dependence of pure RT on Δj. For VRT to (001) the constraint-induced restrictions on bnmax are incorporated quantitatively and the vibrational channel-opening velocity is treated as a vector quantity. The results of these calculations are in good agreement with experiment. The underlying mechanism, likely to be general in VRT, is clearly revealed in plots of relative velocity versus rotational AM change.

Connecting synthetic chemistry decisions to cell and genome biology using small-molecule phenotypic profiling

PubMed Central

Wagner, Bridget K.; Clemons, Paul A.

2009-01-01

Discovering small-molecule modulators for thousands of gene products requires multiple stages of biological testing, specificity evaluation, and chemical optimization. Many cellular profiling methods, including cellular sensitivity, gene-expression, and cellular imaging, have emerged as methods to assess the functional consequences of biological perturbations. Cellular profiling methods applied to small-molecule science provide opportunities to use complex phenotypic information to prioritize and optimize small-molecule structures simultaneously against multiple biological endpoints. As throughput increases and cost decreases for such technologies, we see an emerging paradigm of using more information earlier in probe- and drug-discovery efforts. Moreover, increasing access to public datasets makes possible the construction of “virtual” profiles of small-molecule performance, even when multiplexed measurements were not performed or when multidimensional profiling was not the original intent. We review some key conceptual advances in small-molecule phenotypic profiling, emphasizing connections to other information, such as protein-binding measurements, genetic perturbations, and cell states. We argue that to maximally leverage these measurements in probe and drug discovery requires a fundamental connection to synthetic chemistry, allowing the consequences of synthetic decisions to be described in terms of changes in small-molecule profiles. Mining such data in the context of chemical structure and synthesis strategies can inform decisions about chemistry procurement and library development, leading to optimal small-molecule screening collections. PMID:19825513

Small Molecule based Musculoskeletal Regenerative Engineering

PubMed Central

Lo, Kevin W.-H.; Jiang, Tao; Gagnon, Keith A.; Nelson, Clarke; Laurencin, Cato T.

2014-01-01

Clinicians and scientists working in the field of regenerative engineering are actively investigating a wide range of methods to promote musculoskeletal tissue regeneration. Small molecule-mediated tissue regeneration is emerging as a promising strategy for regenerating various musculoskeletal tissues and a large number of small molecule compounds have been recently discovered as potential bioactive molecules for musculoskeletal tissue repair and regeneration. In this review, we summarize the recent literature encompassing the past four years in the area of small bioactive molecule for promoting repair and regeneration of various musculoskeletal tissues including bone, muscle, cartilage, tendon, and nerve. PMID:24405851

Defining RNA–Small Molecule Affinity Landscapes Enables Design of a Small Molecule Inhibitor of an Oncogenic Noncoding RNA

PubMed Central

2017-01-01

RNA drug targets are pervasive in cells, but methods to design small molecules that target them are sparse. Herein, we report a general approach to score the affinity and selectivity of RNA motif–small molecule interactions identified via selection. Named High Throughput Structure–Activity Relationships Through Sequencing (HiT-StARTS), HiT-StARTS is statistical in nature and compares input nucleic acid sequences to selected library members that bind a ligand via high throughput sequencing. The approach allowed facile definition of the fitness landscape of hundreds of thousands of RNA motif–small molecule binding partners. These results were mined against folded RNAs in the human transcriptome and identified an avid interaction between a small molecule and the Dicer nuclease-processing site in the oncogenic microRNA (miR)-18a hairpin precursor, which is a member of the miR-17-92 cluster. Application of the small molecule, Targapremir-18a, to prostate cancer cells inhibited production of miR-18a from the cluster, de-repressed serine/threonine protein kinase 4 protein (STK4), and triggered apoptosis. Profiling the cellular targets of Targapremir-18a via Chemical Cross-Linking and Isolation by Pull Down (Chem-CLIP), a covalent small molecule–RNA cellular profiling approach, and other studies showed specific binding of the compound to the miR-18a precursor, revealing broadly applicable factors that govern small molecule drugging of noncoding RNAs. PMID:28386598

Understanding the Halogenation Effects in Diketopyrrolopyrrole-Based Small Molecule Photovoltaics.

PubMed

Sun, Shi-Xin; Huo, Yong; Li, Miao-Miao; Hu, Xiaowen; Zhang, Hai-Jun; Zhang, You-Wen; Zhang, You-Dan; Chen, Xiao-Long; Shi, Zi-Fa; Gong, Xiong; Chen, Yongsheng; Zhang, Hao-Li

2015-09-16

Two molecules containing a central diketopyrrolopyrrole and two oligothiophene units have been designed and synthesized. Comparisons between the molecules containing terminal F (FDPP) and Cl (CDPP) atoms allowed us to evaluate the effects of halogenation on the photovoltaic properties of the small molecule organic solar cells (OSCs). The OSCs devices employing FDPP:PC71BM films showed power conversion efficiencies up to 4.32%, suggesting that fluorination is an efficient method for constructing small molecules for OSCs.

ChemBank: a small-molecule screening and cheminformatics resource database.

PubMed

Seiler, Kathleen Petri; George, Gregory A; Happ, Mary Pat; Bodycombe, Nicole E; Carrinski, Hyman A; Norton, Stephanie; Brudz, Steve; Sullivan, John P; Muhlich, Jeremy; Serrano, Martin; Ferraiolo, Paul; Tolliday, Nicola J; Schreiber, Stuart L; Clemons, Paul A

2008-01-01

ChemBank (http://chembank.broad.harvard.edu/) is a public, web-based informatics environment developed through a collaboration between the Chemical Biology Program and Platform at the Broad Institute of Harvard and MIT. This knowledge environment includes freely available data derived from small molecules and small-molecule screens and resources for studying these data. ChemBank is unique among small-molecule databases in its dedication to the storage of raw screening data, its rigorous definition of screening experiments in terms of statistical hypothesis testing, and its metadata-based organization of screening experiments into projects involving collections of related assays. ChemBank stores an increasingly varied set of measurements derived from cells and other biological assay systems treated with small molecules. Analysis tools are available and are continuously being developed that allow the relationships between small molecules, cell measurements, and cell states to be studied. Currently, ChemBank stores information on hundreds of thousands of small molecules and hundreds of biomedically relevant assays that have been performed at the Broad Institute by collaborators from the worldwide research community. The goal of ChemBank is to provide life scientists unfettered access to biomedically relevant data and tools heretofore available primarily in the private sector.

Highly Resolved Studies of Vacuum Ultraviolet Photoionization Dynamics

NASA Astrophysics Data System (ADS)

Kakar, Sandeep

We use measurements of dispersed fluorescence from electronically excited photoions to study fundamental aspects of intramolecular dynamics. Our experimental innovations make it possible to obtain highly resolved photoionization data that offer qualitative insights into molecular scattering. In particular, we obtain vibrationally resolved data to probe coupling between the electronic and nuclear degrees of freedom by studying the distribution of vibrational energy among photoions. Vibrationally resolved branching ratios are measured over a broad spectral range of excitation energy and their non-Franck-Condon behavior is used as a tool to investigate two diverse aspects of shape resonant photoionization. First, vibrational branching ratios are obtained for the SiF_4 5a _1^{-1} and CS_2 5sigma_{rm u} ^{-1} photoionization channels to help elucidate the microscopic aspects of shape resonant wavefunction for polyatomic molecules. It is shown that in such molecules the shape resonant wavefunction is not necessarily attributable to a specific bond in the molecule. Second, the multichannel aspect of shape resonant photoionization dynamics, reflected in continuum channel coupling, is investigated by obtaining vibrational branching ratios for the 2 sigma_{rm u}^{ -1} and 4sigma^{ -1} photoionization of the isoelectronic molecules N_2 and CO, respectively. These data indicate that effects of continuum coupling may be widespread. We also present the first set of rotationally resolved data over a wide energy range for the 2 sigma_{rm u}^{ -1} photoionization of N_2. These data probe the partitioning of the angular momentum between the photoelectron and photoion, and highlight the multicenter nature of the molecular potential. These case studies illustrate the utility of dispersed fluorescence measurements as a complement to photoelectron spectroscopy for obtaining highly resolved data for molecular photoionization. These measurements makes it possible to probe intrinsically molecular aspects, such as the vibration and rotation, of photoionization dynamics over an extended spectral range when used in conjunction with synchrotron radiation as the exciting source. Furthermore, the high resolution made possible by this technique provides high selectivity for accessing weaker ionization channels which are the ones strongly affected by resonant activity, and the present study repeatedly stresses the importance of this capability in discovering and deciphering new trends in resonant molecular ionization dynamics.

Harnessing Connectivity in a Large-Scale Small-Molecule Sensitivity Dataset | Office of Cancer Genomics

Cancer.gov

Identifying genetic alterations that prime a cancer cell to respond to a particular therapeutic agent can facilitate the development of precision cancer medicines. Cancer cell-line (CCL) profiling of small-molecule sensitivity has emerged as an unbiased method to assess the relationships between genetic or cellular features of CCLs and small-molecule response. Here, we developed annotated cluster multidimensional enrichment analysis to explore the associations between groups of small molecules and groups of CCLs in a new, quantitative sensitivity dataset.

A Nonfullerene Small Molecule Acceptor with 3D Interlocking Geometry Enabling Efficient Organic Solar Cells.

PubMed

Lee, Jaewon; Singh, Ranbir; Sin, Dong Hun; Kim, Heung Gyu; Song, Kyu Chan; Cho, Kilwon

2016-01-06

A new 3D nonfullerene small-molecule acceptor is reported. The 3D interlocking geometry of the small-molecule acceptor enables uniform molecular conformation and strong intermolecular connectivity, facilitating favorable nanoscale phase separation and electron charge transfer. By employing both a novel polymer donor and a nonfullerene small-molecule acceptor in the solution-processed organic solar cells, a high-power conversion efficiency of close to 6% is demonstrated. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A "roller-wheel" Pt-containing small molecule that outperforms its polymer analogs in organic solar cells

DOE PAGES

He, Wenhan; Wu, Qin; Livshits, Maksim Y.; ...

2016-05-23

A novel Pt-bisacetylide small molecule (Pt-SM) featuring “roller-wheel” geometry was synthesized and characterized. When compared with conventional Pt-containing polymers and small molecules having “dumbbell” shaped structures, Pt-SM displays enhanced crystallinity and intermolecular π–π interactions, as well as favorable panchromatic absorption behaviors. Furthermore, organic solar cells (OSCs) employing Pt-SM achieve power conversion efficiencies (PCEs) up to 5.9%, the highest reported so far for Pt-containing polymers and small molecules.

A "roller-wheel" Pt-containing small molecule that outperforms its polymer analogs in organic solar cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

He, Wenhan; Wu, Qin; Livshits, Maksim Y.

A novel Pt-bisacetylide small molecule (Pt-SM) featuring “roller-wheel” geometry was synthesized and characterized. When compared with conventional Pt-containing polymers and small molecules having “dumbbell” shaped structures, Pt-SM displays enhanced crystallinity and intermolecular π–π interactions, as well as favorable panchromatic absorption behaviors. Furthermore, organic solar cells (OSCs) employing Pt-SM achieve power conversion efficiencies (PCEs) up to 5.9%, the highest reported so far for Pt-containing polymers and small molecules.

A-π-D-π-A Electron-Donating Small Molecules for Solution-Processed Organic Solar Cells: A Review.

PubMed

Wang, Zhen; Zhu, Lingyun; Shuai, Zhigang; Wei, Zhixiang

2017-11-01

Organic solar cells based on semiconducting polymers and small molecules have attracted considerable attention in the last two decades. Moreover, the power conversion efficiencies for solution-processed solar cells containing A-π-D-π-A-type small molecules and fullerenes have reached 11%. However, the method for designing high-performance, photovoltaic small molecules still remains unclear. In this review, recent studies on A-π-D-π-A electron-donating small molecules for organic solar cells are introduced. Moreover, the relationships between molecular properties and device performances are summarized, from which inspiration for the future design of high performance organic solar cells may be obtained. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Ab initio multiple spawning dynamics study of dimethylnitramine and dimethylnitramine-Fe complex to model their ultrafast nonadiabatic chemistry

NASA Astrophysics Data System (ADS)

Bera, Anupam; Ghosh, Jayanta; Bhattacharya, Atanu

2017-07-01

Conical intersections are now firmly established to be the key features in the excited electronic state processes of polyatomic energetic molecules. In the present work, we have explored conical intersection-mediated nonadiabatic chemical dynamics of a simple analogue nitramine molecule, dimethylnitramine (DMNA, containing one N-NO2 energetic group), and its complex with an iron atom (DMNA-Fe). For this task, we have used the ab initio multiple spawning (AIMS) dynamics simulation at the state averaged-complete active space self-consistent field(8,5)/6-31G(d) level of theory. We have found that DMNA relaxes back to the ground (S0) state following electronic excitation to the S1 excited state [which is an (n,π*) excited state] with a time constant of approximately 40 fs. This AIMS result is in very good agreement with the previous surface hopping-result and femtosecond laser spectroscopy result. DMNA does not dissociate during this fast internal conversion from the S1 to the S0 state. DMNA-Fe also undergoes extremely fast relaxation from the upper S1 state to the S0 state; however, this relaxation pathway is dissociative in nature. DMNA-Fe undergoes initial Fe-O, N-O, and N-N bond dissociations during relaxation from the upper S1 state to the ground S0 state through the respective conical intersection. The AIMS simulation reveals the branching ratio of these three channels as N-N:Fe-O:N-O = 6:3:1 (based on 100 independent simulations). Furthermore, the AIMS simulation reveals that the Fe-O bond dissociation channel exhibits the fastest (time constant 24 fs) relaxation, while the N-N bond dissociation pathway features the slowest (time constant 128 fs) relaxation. An intermediate time constant (30 fs) is found for the N-O bond dissociation channel. This is the first nonadiabatic chemical dynamics study of metal-contained energetic molecules through conical intersections.

Science at the Time-scale of the Electron

NASA Astrophysics Data System (ADS)

Murnane, Margaret

2010-03-01

Replace this text with your abstract Ever since the invention of the laser 50 years ago and its application in nonlinear optics, scientists have been striving to extend coherent laser beams into the x-ray region of the spectrum. Very recently however, the prospects for tabletop coherent sources, with attosecond pulse durations, at very short wavelengths even in the hard x-ray region of the spectrum at wavelengths < 1nm, have brightened considerably. These advances are possible by taking nonlinear optics techniques to an extreme, and are the direct result of a new ability to manipulate electrons on the fastest, attosecond, time-scales of our natural world. My talk will discuss new experimental data that demonstrates high harmonic generation of laser-like, fully coherent, 10 attosecond duration, soft x-ray beams at photon energies around 0.5keV. Several applications will also be discussed, including making a movie of how electron orbitals in a molecule change shape as a molecule breaks apart, following how fast a magnetic material can flip orientation, understanding how fast heat flows in a nanocircuit, or building a microscope without lenses. [4pt] [1] T. Popmintchev et al., ``Phase matched upconversion of coherent ultrafast laser light into the soft and hard x-ray regions of the spectrum'', PNAS 106, 10516 (2009). [0pt] [2] C. LaOVorakiat et al., ``Ultrafast Soft X-Ray Magneto-Optics at the M-edge Using a Tabletop High-Harmonic Source'', Physical Review Letters 103, 257402 (2009). [0pt] [3] M. Siemens et al. ``Measurement of quasi-ballistic heat transport across nanoscale interfaces using ultrafast coherent soft x-ray beams'', Nature Materials 9, 26 (2010). [0pt] [4] K. Raines et al., ``Three-dimensional structure determination from a single view,'' Nature 463, 214 (2010). [0pt] [5] W. Li et al., ``Time-resolved Probing of Dynamics in Polyatomic Molecules using High Harmonic Generation'', Science 322, 1207 (2008).

A general electrochemical method for label-free screening of protein–small molecule interactions†

PubMed Central

Cash, Kevin J.; Ricci, Francesco

2010-01-01

Here we report a versatile method by which the interaction between a protein and a small molecule, and the disruption of that interaction by competition with other small molecules, can be monitored electrochemically directly in complex sample matrices. PMID:19826675

Toward Generalization of Iterative Small Molecule Synthesis

PubMed Central

Lehmann, Jonathan W.; Blair, Daniel J.; Burke, Martin D.

2018-01-01

Small molecules have extensive untapped potential to benefit society, but access to this potential is too often restricted by limitations inherent to the customized approach currently used to synthesize this class of chemical matter. In contrast, the “building block approach”, i.e., generalized iterative assembly of interchangeable parts, has now proven to be a highly efficient and flexible way to construct things ranging all the way from skyscrapers to macromolecules to artificial intelligence algorithms. The structural redundancy found in many small molecules suggests that they possess a similar capacity for generalized building block-based construction. It is also encouraging that many customized iterative synthesis methods have been developed that improve access to specific classes of small molecules. There has also been substantial recent progress toward the iterative assembly of many different types of small molecules, including complex natural products, pharmaceuticals, biological probes, and materials, using common building blocks and coupling chemistry. Collectively, these advances suggest that a generalized building block approach for small molecule synthesis may be within reach. PMID:29696152

Screening of Small Molecule Interactor Library by Using In-Cell NMR Spectroscopy (SMILI-NMR)

PubMed Central

Xie, Jingjing; Thapa, Rajiv; Reverdatto, Sergey; Burz, David S.; Shekhtman, Alexander

2011-01-01

We developed an in-cell NMR assay for screening small molecule interactor libraries (SMILI-NMR) for compounds capable of disrupting or enhancing specific interactions between two or more components of a biomolecular complex. The method relies on the formation of a well-defined biocomplex and utilizes in-cell NMR spectroscopy to identify the molecular surfaces involved in the interaction at atomic scale resolution. Changes in the interaction surface caused by a small molecule interfering with complex formation are used as a read-out of the assay. The in-cell nature of the experimental protocol insures that the small molecule is capable of penetrating the cell membrane and specifically engaging the target molecule(s). Utility of the method was demonstrated by screening a small dipeptide library against the FKBP–FRB protein complex involved in cell cycle arrest. The dipeptide identified by SMILI-NMR showed biological activity in a functional assay in yeast. PMID:19422228

The effect of aged litter materials on polyatomic ion concentrations in fractionated suspended particulate matter from broiler house

USDA-ARS?s Scientific Manuscript database

Inorganic emissions from livestock production and subsequent deposition of these ions can be a major source of pollution, causing nitrogen enrichment, eutrophication, acidification of soils and surface waters, and aerosol formation. In the poultry house, ammonia and hydrogen sulfide emissions can a...

Interactions of quercetin, curcumin, epigallocatechin gallate and folic acid with gelatin.

PubMed

Yang, Tingting; Yang, Huiru; Fan, Yan; Li, Bafang; Hou, Hu

2018-06-15

Some small bioactive molecules from food show the potential health benefits, but with poor chemical stability and bioavailability. The interactions between small molecules and gelatin were investigated. Fluorescence experiments demonstrated that the bimolecular quenching constants (k q ) of complexes (gelatin-quercetin, gelatin-curcumin, gelatin-epigallocatechin gallate, gelatin-folic acid) were 3.7 × 10 12  L·mol -1 ·s -1 , 1.4 × 10 12  L·mol -1 ·s -1 , 2.7 × 10 12  L·mol -1 ·s -1 and 8.5 × 10 12  L·mol -1 ·s -1 , indicating that fluorescence quenching did not arise from a dynamical mechanism, but from gelatin-small molecules binding. Furthermore, the affinity with gelatin was ranked in the order of folic acid > quercetin > epigallocatechin gallate > curcumin. Fluorescence spectroscopy, ultraviolet and visible absorption spectroscopy, FTIR and circular dichroism showed that the interactions between small molecules and gelatin did not significantly alter the conformation and secondary structure of gelatin. Non-covalent interactions may result in the binding of gelatin with small molecules. The interactions were considered to be through two modes: (1) small molecules bound within the hydrophobic pockets of gelatin; (2) small molecules surrounded the gelatin molecule mainly through hydrogen bonds and hydrophobic interactions. Copyright © 2018 Elsevier B.V. All rights reserved.

Ion dehydration controls adsorption at the micellar interface: hydrotropic ions.

PubMed

Lima, Filipe S; Andrade, Marcos F C; Mortara, Laura; Gustavo Dias, Luís; Cuccovia, Iolanda M; Chaimovich, Hernan

2017-11-22

The properties of ionic micelles depend on the nature of the counterion, and these effects become more evident as the ion adsorption at the interface increases. Prediction of the relative extent of ion adsorption is required for rational design of ionic micellar aggregates. Unlike the well understood adsorption of monatomic ions, the adsorption of polyatomic ions is not easily predicted. We combined experimental and computational methods to evaluate the affinity of hydrotropic ions, i.e., ions with polar and apolar regions, to the surface of positively charged micelles. We analyzed cationic micelles of dodecyltrimethylammonium and six hydrotropic counterions: methanesulfonate, trifluoromethanesulfonate, benzenesulfonate, acetate, trifluoroacetate and benzoate. Our results demonstrated that the apolar region of hydrotropic ions had the largest influence on micellar properties. The dehydration of the apolar region of hydrotropic ions upon their adsorption at the micellar interface determined the ion adsorption extension, differently to what was expected based on Collins' law of matching affinities. These results may lead to more general models to describe the adsorption of ions, including polyatomic ions, at the micellar interface.

Selection and Biosensor Application of Aptamers for Small Molecules

PubMed Central

Pfeiffer, Franziska; Mayer, Günter

2016-01-01

Small molecules play a major role in the human body and as drugs, toxins, and chemicals. Tools to detect and quantify them are therefore in high demand. This review will give an overview about aptamers interacting with small molecules and their selection. We discuss the current state of the field, including advantages as well as problems associated with their use and possible solutions to tackle these. We then discuss different kinds of small molecule aptamer-based sensors described in literature and their applications, ranging from detecting drinking water contaminations to RNA imaging. PMID:27379229

Methods to enable the design of bioactive small molecules targeting RNA

PubMed Central

Disney, Matthew D.; Yildirim, Ilyas; Childs-Disney, Jessica L.

2014-01-01

RNA is an immensely important target for small molecule therapeutics or chemical probes of function. However, methods that identify, annotate, and optimize RNA-small molecule interactions that could enable the design of compounds that modulate RNA function are in their infancies. This review describes recent approaches that have been developed to understand and optimize RNA motif-small molecule interactions, including Structure-Activity Relationships Through Sequencing (StARTS), quantitative structure-activity relationships (QSAR), chemical similarity searching, structure-based design and docking, and molecular dynamics (MD) simulations. Case studies described include the design of small molecules targeting RNA expansions, the bacterial A-site, viral RNAs, and telomerase RNA. These approaches can be combined to afford a synergistic method to exploit the myriad of RNA targets in the transcriptome. PMID:24357181

Methods to enable the design of bioactive small molecules targeting RNA.

PubMed

Disney, Matthew D; Yildirim, Ilyas; Childs-Disney, Jessica L

2014-02-21

RNA is an immensely important target for small molecule therapeutics or chemical probes of function. However, methods that identify, annotate, and optimize RNA-small molecule interactions that could enable the design of compounds that modulate RNA function are in their infancies. This review describes recent approaches that have been developed to understand and optimize RNA motif-small molecule interactions, including structure-activity relationships through sequencing (StARTS), quantitative structure-activity relationships (QSAR), chemical similarity searching, structure-based design and docking, and molecular dynamics (MD) simulations. Case studies described include the design of small molecules targeting RNA expansions, the bacterial A-site, viral RNAs, and telomerase RNA. These approaches can be combined to afford a synergistic method to exploit the myriad of RNA targets in the transcriptome.

Harnessing Connectivity in a Large-Scale Small-Molecule Sensitivity Dataset.

PubMed

Seashore-Ludlow, Brinton; Rees, Matthew G; Cheah, Jaime H; Cokol, Murat; Price, Edmund V; Coletti, Matthew E; Jones, Victor; Bodycombe, Nicole E; Soule, Christian K; Gould, Joshua; Alexander, Benjamin; Li, Ava; Montgomery, Philip; Wawer, Mathias J; Kuru, Nurdan; Kotz, Joanne D; Hon, C Suk-Yee; Munoz, Benito; Liefeld, Ted; Dančík, Vlado; Bittker, Joshua A; Palmer, Michelle; Bradner, James E; Shamji, Alykhan F; Clemons, Paul A; Schreiber, Stuart L

2015-11-01

Identifying genetic alterations that prime a cancer cell to respond to a particular therapeutic agent can facilitate the development of precision cancer medicines. Cancer cell-line (CCL) profiling of small-molecule sensitivity has emerged as an unbiased method to assess the relationships between genetic or cellular features of CCLs and small-molecule response. Here, we developed annotated cluster multidimensional enrichment analysis to explore the associations between groups of small molecules and groups of CCLs in a new, quantitative sensitivity dataset. This analysis reveals insights into small-molecule mechanisms of action, and genomic features that associate with CCL response to small-molecule treatment. We are able to recapitulate known relationships between FDA-approved therapies and cancer dependencies and to uncover new relationships, including for KRAS-mutant cancers and neuroblastoma. To enable the cancer community to explore these data, and to generate novel hypotheses, we created an updated version of the Cancer Therapeutic Response Portal (CTRP v2). We present the largest CCL sensitivity dataset yet available, and an analysis method integrating information from multiple CCLs and multiple small molecules to identify CCL response predictors robustly. We updated the CTRP to enable the cancer research community to leverage these data and analyses. ©2015 American Association for Cancer Research.

Fundamental and methodological investigations for the improvement of elemental analysis by inductively coupled plasma mass soectrometry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ebert, Christopher Hysjulien

This dissertation describes a variety of studies meant to improve the analytical performance of inductively coupled plasma mass spectrometry (ICP-MS) and laser ablation (LA) ICP-MS. The emission behavior of individual droplets and LA generated particles in an ICP is studied using a high-speed, high frame rate digital camera. Phenomena are observed during the ablation of silicate glass that would cause elemental fractionation during analysis by ICP-MS. Preliminary work for ICP torch developments specifically tailored for the improvement of LA sample introduction are presented. An abnormal scarcity of metal-argon polyatomic ions (MAr{sup +}) is observed during ICP-MS analysis. Evidence shows thatmore » MAr{sup +} ions are dissociated by collisions with background gas in a shockwave near the tip of the skimmer cone. Method development towards the improvement of LA-ICP-MS for environmental monitoring is described. A method is developed to trap small particles in a collodion matrix and analyze each particle individually by LA-ICP-MS.« less

Identification of a Broad-Spectrum Antiviral Small Molecule against Severe Acute Respiratory Syndrome Coronavirus and Ebola, Hendra, and Nipah Viruses by Using a Novel High-Throughput Screening Assay

PubMed Central

Elshabrawy, Hatem A.; Fan, Jilao; Haddad, Christine S.; Ratia, Kiira; Broder, Christopher C.; Caffrey, Michael

2014-01-01

ABSTRACT Severe acute respiratory syndrome coronavirus (SARS-CoV) and Ebola, Hendra, and Nipah viruses are members of different viral families and are known causative agents of fatal viral diseases. These viruses depend on cathepsin L for entry into their target cells. The viral glycoproteins need to be primed by protease cleavage, rendering them active for fusion with the host cell membrane. In this study, we developed a novel high-throughput screening assay based on peptides, derived from the glycoproteins of the aforementioned viruses, which contain the cathepsin L cleavage site. We screened a library of 5,000 small molecules and discovered a small molecule that can inhibit the cathepsin L cleavage of all viral peptides with minimal inhibition of cleavage of a host protein-derived peptide (pro-neuropeptide Y). The small molecule inhibited the entry of all pseudotyped viruses in vitro and the cleavage of SARS-CoV spike glycoprotein in an in vitro cleavage assay. In addition, the Hendra and Nipah virus fusion glycoproteins were not cleaved in the presence of the small molecule in a cell-based cleavage assay. Furthermore, we demonstrate that the small molecule is a mixed inhibitor of cathepsin L. Our broad-spectrum antiviral small molecule appears to be an ideal candidate for future optimization and development into a potent antiviral against SARS-CoV and Ebola, Hendra, and Nipah viruses. IMPORTANCE We developed a novel high-throughput screening assay to identify small molecules that can prevent cathepsin L cleavage of viral glycoproteins derived from SARS-CoV and Ebola, Hendra, and Nipah viruses that are required for their entry into the host cell. We identified a novel broad-spectrum small molecule that could block cathepsin L-mediated cleavage and thus inhibit the entry of pseudotypes bearing the glycoprotein derived from SARS-CoV or Ebola, Hendra, or Nipah virus. The small molecule can be further optimized and developed into a potent broad-spectrum antiviral drug. PMID:24501399

Identification of a broad-spectrum antiviral small molecule against severe acute respiratory syndrome coronavirus and Ebola, Hendra, and Nipah viruses by using a novel high-throughput screening assay.

PubMed

Elshabrawy, Hatem A; Fan, Jilao; Haddad, Christine S; Ratia, Kiira; Broder, Christopher C; Caffrey, Michael; Prabhakar, Bellur S

2014-04-01

Severe acute respiratory syndrome coronavirus (SARS-CoV) and Ebola, Hendra, and Nipah viruses are members of different viral families and are known causative agents of fatal viral diseases. These viruses depend on cathepsin L for entry into their target cells. The viral glycoproteins need to be primed by protease cleavage, rendering them active for fusion with the host cell membrane. In this study, we developed a novel high-throughput screening assay based on peptides, derived from the glycoproteins of the aforementioned viruses, which contain the cathepsin L cleavage site. We screened a library of 5,000 small molecules and discovered a small molecule that can inhibit the cathepsin L cleavage of all viral peptides with minimal inhibition of cleavage of a host protein-derived peptide (pro-neuropeptide Y). The small molecule inhibited the entry of all pseudotyped viruses in vitro and the cleavage of SARS-CoV spike glycoprotein in an in vitro cleavage assay. In addition, the Hendra and Nipah virus fusion glycoproteins were not cleaved in the presence of the small molecule in a cell-based cleavage assay. Furthermore, we demonstrate that the small molecule is a mixed inhibitor of cathepsin L. Our broad-spectrum antiviral small molecule appears to be an ideal candidate for future optimization and development into a potent antiviral against SARS-CoV and Ebola, Hendra, and Nipah viruses. We developed a novel high-throughput screening assay to identify small molecules that can prevent cathepsin L cleavage of viral glycoproteins derived from SARS-CoV and Ebola, Hendra, and Nipah viruses that are required for their entry into the host cell. We identified a novel broad-spectrum small molecule that could block cathepsin L-mediated cleavage and thus inhibit the entry of pseudotypes bearing the glycoprotein derived from SARS-CoV or Ebola, Hendra, or Nipah virus. The small molecule can be further optimized and developed into a potent broad-spectrum antiviral drug.

Recent Developments in β-Cell Differentiation of Pluripotent Stem Cells Induced by Small and Large Molecules

PubMed Central

Kumar, S. Suresh; Alarfaj, Abdullah A.; Munusamy, Murugan A.; Singh, A. J. A. Ranjith; Peng, I-Chia; Priya, Sivan Padma; Hamat, Rukman Awang; Higuchi, Akon

2014-01-01

Human pluripotent stem cells, including human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs), hold promise as novel therapeutic tools for diabetes treatment because of their self-renewal capacity and ability to differentiate into beta (β)-cells. Small and large molecules play important roles in each stage of β-cell differentiation from both hESCs and hiPSCs. The small and large molecules that are described in this review have significantly advanced efforts to cure diabetic disease. Lately, effective protocols have been implemented to induce hESCs and human mesenchymal stem cells (hMSCs) to differentiate into functional β-cells. Several small molecules, proteins, and growth factors promote pancreatic differentiation from hESCs and hMSCs. These small molecules (e.g., cyclopamine, wortmannin, retinoic acid, and sodium butyrate) and large molecules (e.g. activin A, betacellulin, bone morphogentic protein (BMP4), epidermal growth factor (EGF), fibroblast growth factor (FGF), keratinocyte growth factor (KGF), hepatocyte growth factor (HGF), noggin, transforming growth factor (TGF-α), and WNT3A) are thought to contribute from the initial stages of definitive endoderm formation to the final stages of maturation of functional endocrine cells. We discuss the importance of such small and large molecules in uniquely optimized protocols of β-cell differentiation from stem cells. A global understanding of various small and large molecules and their functions will help to establish an efficient protocol for β-cell differentiation. PMID:25526563

High Throughput, Label-free Screening Small Molecule Compound Libraries for Protein-Ligands using Combination of Small Molecule Microarrays and a Special Ellipsometry-based Optical Scanner.

PubMed

Landry, James P; Fei, Yiyan; Zhu, X D

2011-12-01

Small-molecule compounds remain the major source of therapeutic and preventative drugs. Developing new drugs against a protein target often requires screening large collections of compounds with diverse structures for ligands or ligand fragments that exhibit sufficiently affinity and desirable inhibition effect on the target before further optimization and development. Since the number of small molecule compounds is large, high-throughput screening (HTS) methods are needed. Small-molecule microarrays (SMM) on a solid support in combination with a suitable binding assay form a viable HTS platform. We demonstrate that by combining an oblique-incidence reflectivity difference optical scanner with SMM we can screen 10,000 small-molecule compounds on a single glass slide for protein ligands without fluorescence labeling. Furthermore using such a label-free assay platform we can simultaneously acquire binding curves of a solution-phase protein to over 10,000 immobilized compounds, thus enabling full characterization of protein-ligand interactions over a wide range of affinity constants.

Delivery of small molecules for bone regenerative engineering: preclinical studies and potential clinical applications.

PubMed

Laurencin, Cato T; Ashe, Keshia M; Henry, Nicole; Kan, Ho Man; Lo, Kevin W-H

2014-06-01

Stimulation of bone regeneration using growth factors is a promising approach for musculoskeletal regenerative engineering. However, common limitations with protein growth factors, such as high manufacturing costs, protein instability, contamination issues, and unwanted immunogenic responses of the host reduce potential clinical applications. New strategies for bone regeneration that involve inexpensive and stable small molecules can obviate these problems and have a significant impact on the treatment of skeletal injury and diseases. Over the past decade, a large number of small molecules with the potential of regenerating skeletal tissue have been reported in the literature. Here, we review this literature, paying specific attention to the prospects for small molecule-based bone-regenerative engineering. We also review the preclinical study of small molecules associated with bone regeneration. Copyright © 2014 Elsevier Ltd. All rights reserved.

Small molecule annotation for the Protein Data Bank

PubMed Central

Sen, Sanchayita; Young, Jasmine; Berrisford, John M.; Chen, Minyu; Conroy, Matthew J.; Dutta, Shuchismita; Di Costanzo, Luigi; Gao, Guanghua; Ghosh, Sutapa; Hudson, Brian P.; Igarashi, Reiko; Kengaku, Yumiko; Liang, Yuhe; Peisach, Ezra; Persikova, Irina; Mukhopadhyay, Abhik; Narayanan, Buvaneswari Coimbatore; Sahni, Gaurav; Sato, Junko; Sekharan, Monica; Shao, Chenghua; Tan, Lihua; Zhuravleva, Marina A.

2014-01-01

The Protein Data Bank (PDB) is the single global repository for three-dimensional structures of biological macromolecules and their complexes, and its more than 100 000 structures contain more than 20 000 distinct ligands or small molecules bound to proteins and nucleic acids. Information about these small molecules and their interactions with proteins and nucleic acids is crucial for our understanding of biochemical processes and vital for structure-based drug design. Small molecules present in a deposited structure may be attached to a polymer or may occur as a separate, non-covalently linked ligand. During curation of a newly deposited structure by wwPDB annotation staff, each molecule is cross-referenced to the PDB Chemical Component Dictionary (CCD). If the molecule is new to the PDB, a dictionary description is created for it. The information about all small molecule components found in the PDB is distributed via the ftp archive as an external reference file. Small molecule annotation in the PDB also includes information about ligand-binding sites and about covalent and other linkages between ligands and macromolecules. During the remediation of the peptide-like antibiotics and inhibitors present in the PDB archive in 2011, it became clear that additional annotation was required for consistent representation of these molecules, which are quite often composed of several sequential subcomponents including modified amino acids and other chemical groups. The connectivity information of the modified amino acids is necessary for correct representation of these biologically interesting molecules. The combined information is made available via a new resource called the Biologically Interesting molecules Reference Dictionary, which is complementary to the CCD and is now routinely used for annotation of peptide-like antibiotics and inhibitors. PMID:25425036

Small molecule annotation for the Protein Data Bank.

PubMed

Sen, Sanchayita; Young, Jasmine; Berrisford, John M; Chen, Minyu; Conroy, Matthew J; Dutta, Shuchismita; Di Costanzo, Luigi; Gao, Guanghua; Ghosh, Sutapa; Hudson, Brian P; Igarashi, Reiko; Kengaku, Yumiko; Liang, Yuhe; Peisach, Ezra; Persikova, Irina; Mukhopadhyay, Abhik; Narayanan, Buvaneswari Coimbatore; Sahni, Gaurav; Sato, Junko; Sekharan, Monica; Shao, Chenghua; Tan, Lihua; Zhuravleva, Marina A

2014-01-01

The Protein Data Bank (PDB) is the single global repository for three-dimensional structures of biological macromolecules and their complexes, and its more than 100,000 structures contain more than 20,000 distinct ligands or small molecules bound to proteins and nucleic acids. Information about these small molecules and their interactions with proteins and nucleic acids is crucial for our understanding of biochemical processes and vital for structure-based drug design. Small molecules present in a deposited structure may be attached to a polymer or may occur as a separate, non-covalently linked ligand. During curation of a newly deposited structure by wwPDB annotation staff, each molecule is cross-referenced to the PDB Chemical Component Dictionary (CCD). If the molecule is new to the PDB, a dictionary description is created for it. The information about all small molecule components found in the PDB is distributed via the ftp archive as an external reference file. Small molecule annotation in the PDB also includes information about ligand-binding sites and about covalent and other linkages between ligands and macromolecules. During the remediation of the peptide-like antibiotics and inhibitors present in the PDB archive in 2011, it became clear that additional annotation was required for consistent representation of these molecules, which are quite often composed of several sequential subcomponents including modified amino acids and other chemical groups. The connectivity information of the modified amino acids is necessary for correct representation of these biologically interesting molecules. The combined information is made available via a new resource called the Biologically Interesting molecules Reference Dictionary, which is complementary to the CCD and is now routinely used for annotation of peptide-like antibiotics and inhibitors. © The Author(s) 2014. Published by Oxford University Press.

Developing an Efficient and General Strategy for Immobilization of Small Molecules onto Microarrays Using Isocyanate Chemistry.

PubMed

Zhu, Chenggang; Zhu, Xiangdong; Landry, James P; Cui, Zhaomeng; Li, Quanfu; Dang, Yongjun; Mi, Lan; Zheng, Fengyun; Fei, Yiyan

2016-03-16

Small-molecule microarray (SMM) is an effective platform for identifying lead compounds from large collections of small molecules in drug discovery, and efficient immobilization of molecular compounds is a pre-requisite for the success of such a platform. On an isocyanate functionalized surface, we studied the dependence of immobilization efficiency on chemical residues on molecular compounds, terminal residues on isocyanate functionalized surface, lengths of spacer molecules, and post-printing treatment conditions, and we identified a set of optimized conditions that enable us to immobilize small molecules with significantly improved efficiencies, particularly for those molecules with carboxylic acid residues that are known to have low isocyanate reactivity. We fabricated microarrays of 3375 bioactive compounds on isocyanate functionalized glass slides under these optimized conditions and confirmed that immobilization percentage is over 73%.

Cell-targetable DNA nanocapsules for spatiotemporal release of caged bioactive small molecules

NASA Astrophysics Data System (ADS)

Veetil, Aneesh T.; Chakraborty, Kasturi; Xiao, Kangni; Minter, Myles R.; Sisodia, Sangram S.; Krishnan, Yamuna

2017-12-01

Achieving triggered release of small molecules with spatial and temporal precision at designated cells within an organism remains a challenge. By combining a cell-targetable, icosahedral DNA-nanocapsule loaded with photoresponsive polymers, we show cytosolic delivery of small molecules with the spatial resolution of single endosomes in specific cells in Caenorhabditis elegans. Our technology can report on the extent of small molecules released after photoactivation as well as pinpoint the location at which uncaging of the molecules occurred. We apply this technology to release dehydroepiandrosterone (DHEA), a neurosteroid that promotes neurogenesis and neuron survival, and determined the timescale of neuronal activation by DHEA, using light-induced release of DHEA from targeted DNA nanocapsules. Importantly, sequestration inside the DNA capsule prevents photocaged DHEA from activating neurons prematurely. Our methodology can in principle be generalized to diverse neurostimulatory molecules.

Exploring biology with small organic molecules

PubMed Central

Stockwell, Brent R.

2011-01-01

Small organic molecules have proven to be invaluable tools for investigating biological systems, but there is still much to learn from their use. To discover and to use more effectively new chemical tools to understand biology, strategies are needed that allow us to systematically explore ‘biological-activity space’. Such strategies involve analysing both protein binding of, and phenotypic responses to, small organic molecules. The mapping of biological-activity space using small molecules is akin to mapping the stars — uncharted territory is explored using a system of coordinates that describes where each new feature lies. PMID:15602550

Study of Polyatomic Dynamics in the Atmosphere.

DTIC Science & Technology

1987-03-25

phere and the Shuttle ram glow. Ihij~pijj erif of th0 . repiir I ds’-vr ihes work carriled nio in the IAIfli V The~ prodi’ j "v of~ t~t electron beam...8217 diatomics-in -mole- Symposium on Molecular Spectroscopy, Ohio State University, Colum- bus , Ohio, June 1935.cules PES for Hj* is used the fundamental

Morphological study on small molecule acceptor-based organic solar cells with efficiencies beyond 7% (Presentation Recording)

NASA Astrophysics Data System (ADS)

Ma, Wei; Yan, He

2015-10-01

Despite the essential role of fullerenes in achieving best-performance organic solar cells (OSCs), fullerene acceptors have several drawbacks including poor light absorption, high-cost production and purification. For this reason, small molecule acceptor (SMA)-based OSCs have attracted much attention due to the easy tunability of electronic and optical properties of SMA materials. In this study, polymers with temperature dependent aggregation behaviors are combined with various small molecule acceptor materials, which lead to impressive power conversion efficiencies of up to 7.3%. The morphological and aggregation properties of the polymer:small molecule blends are studied in details. It is found that the temperature-dependent aggregation behavior of polymers allows for the processing of the polymer solutions at moderately elevated temperature, and more importantly, controlled aggregation and strong crystallization of the polymer during the film cooling and drying process. This results in a well-controlled and near-ideal polymer:small molecule morphology that is controlled by polymer aggregation during warm casting and thus insensitive to the choice of small molecules. As a result, several cases of highly efficient (PCE between 6-7.3%) SMA OSCs are achieved. The second part of this presentation will describe the morphology of a new small molecule acceptor with a unique 3D structure. The relationship between molecular structure and morphology is revealed.

Identification of small molecule inhibitors of cytokinesis and single cell wound repair

PubMed Central

Clark, Andrew G.; Sider, Jenny R.; Verbrugghe, Koen; Fenteany, Gabriel; von Dassow, George; Bement, William M.

2013-01-01

Screening of small molecule libraries offers the potential to identify compounds that inhibit specific biological processes and, ultimately, to identify macromolecules that are important players in such processes. To date, however, most screens of small molecule libraries have focused on identification of compounds that inhibit known proteins or particular steps in a given process, and have emphasized automated primary screens. Here we have used “low tech” in vivo primary screens to identify small molecules that inhibit both cytokinesis and single cell wound repair, two complex cellular processes that possess many common features. The “diversity set”, an ordered array of 1990 compounds available from the National Cancer Institute, was screened in parallel to identify compounds that inhibit cytokinesis in D. excentricus (sand dollar) embryos and single cell wound repair in X. laevis (frog) oocytes. Two small molecules were thus identified: Sph1 and Sph2. Sph1 reduces Rho activation in wound repair and suppresses formation of the spindle midzone during cytokinesis. Sph2 also reduces Rho activation in wound repair and may inhibit cytokinesis by blocking membrane fusion. The results identify two small molecules of interest for analysis of wound repair and cytokinesis, reveal that these processes are more similar than often realized and reveal the potential power of low tech screens of small molecule libraries for analysis of complex cellular processes. PMID:23125193

High-throughput identification and rational design of synergistic small-molecule pairs for combating and bypassing antibiotic resistance.

PubMed

Wambaugh, Morgan A; Shakya, Viplendra P S; Lewis, Adam J; Mulvey, Matthew A; Brown, Jessica C S

2017-06-01

Antibiotic-resistant infections kill approximately 23,000 people and cost $20,000,000,000 each year in the United States alone despite the widespread use of small-molecule antimicrobial combination therapy. Antibiotic combinations typically have an additive effect: the efficacy of the combination matches the sum of the efficacies of each antibiotic when used alone. Small molecules can also act synergistically when the efficacy of the combination is greater than the additive efficacy. However, synergistic combinations are rare and have been historically difficult to identify. High-throughput identification of synergistic pairs is limited by the scale of potential combinations: a modest collection of 1,000 small molecules involves 1 million pairwise combinations. Here, we describe a high-throughput method for rapid identification of synergistic small-molecule pairs, the overlap2 method (O2M). O2M extracts patterns from chemical-genetic datasets, which are created when a collection of mutants is grown in the presence of hundreds of different small molecules, producing a precise set of phenotypes induced by each small molecule across the mutant set. The identification of mutants that show the same phenotype when treated with known synergistic molecules allows us to pinpoint additional molecule combinations that also act synergistically. As a proof of concept, we focus on combinations with the antibiotics trimethoprim and sulfamethizole, which had been standard treatment against urinary tract infections until widespread resistance decreased efficacy. Using O2M, we screened a library of 2,000 small molecules and identified several that synergize with the antibiotic trimethoprim and/or sulfamethizole. The most potent of these synergistic interactions is with the antiviral drug azidothymidine (AZT). We then demonstrate that understanding the molecular mechanism underlying small-molecule synergistic interactions allows the rational design of additional combinations that bypass drug resistance. Trimethoprim and sulfamethizole are both folate biosynthesis inhibitors. We find that this activity disrupts nucleotide homeostasis, which blocks DNA replication in the presence of AZT. Building on these data, we show that other small molecules that disrupt nucleotide homeostasis through other mechanisms (hydroxyurea and floxuridine) also act synergistically with AZT. These novel combinations inhibit the growth and virulence of trimethoprim-resistant clinical Escherichia coli and Klebsiella pneumoniae isolates, suggesting that they may be able to be rapidly advanced into clinical use. In sum, we present a generalizable method to screen for novel synergistic combinations, to identify particular mechanisms resulting in synergy, and to use the mechanistic knowledge to rationally design new combinations that bypass drug resistance.

High-throughput identification and rational design of synergistic small-molecule pairs for combating and bypassing antibiotic resistance

PubMed Central

Lewis, Adam J.; Mulvey, Matthew A.

2017-01-01

Antibiotic-resistant infections kill approximately 23,000 people and cost $20,000,000,000 each year in the United States alone despite the widespread use of small-molecule antimicrobial combination therapy. Antibiotic combinations typically have an additive effect: the efficacy of the combination matches the sum of the efficacies of each antibiotic when used alone. Small molecules can also act synergistically when the efficacy of the combination is greater than the additive efficacy. However, synergistic combinations are rare and have been historically difficult to identify. High-throughput identification of synergistic pairs is limited by the scale of potential combinations: a modest collection of 1,000 small molecules involves 1 million pairwise combinations. Here, we describe a high-throughput method for rapid identification of synergistic small-molecule pairs, the overlap2 method (O2M). O2M extracts patterns from chemical-genetic datasets, which are created when a collection of mutants is grown in the presence of hundreds of different small molecules, producing a precise set of phenotypes induced by each small molecule across the mutant set. The identification of mutants that show the same phenotype when treated with known synergistic molecules allows us to pinpoint additional molecule combinations that also act synergistically. As a proof of concept, we focus on combinations with the antibiotics trimethoprim and sulfamethizole, which had been standard treatment against urinary tract infections until widespread resistance decreased efficacy. Using O2M, we screened a library of 2,000 small molecules and identified several that synergize with the antibiotic trimethoprim and/or sulfamethizole. The most potent of these synergistic interactions is with the antiviral drug azidothymidine (AZT). We then demonstrate that understanding the molecular mechanism underlying small-molecule synergistic interactions allows the rational design of additional combinations that bypass drug resistance. Trimethoprim and sulfamethizole are both folate biosynthesis inhibitors. We find that this activity disrupts nucleotide homeostasis, which blocks DNA replication in the presence of AZT. Building on these data, we show that other small molecules that disrupt nucleotide homeostasis through other mechanisms (hydroxyurea and floxuridine) also act synergistically with AZT. These novel combinations inhibit the growth and virulence of trimethoprim-resistant clinical Escherichia coli and Klebsiella pneumoniae isolates, suggesting that they may be able to be rapidly advanced into clinical use. In sum, we present a generalizable method to screen for novel synergistic combinations, to identify particular mechanisms resulting in synergy, and to use the mechanistic knowledge to rationally design new combinations that bypass drug resistance. PMID:28632788

X-ray characterization of solid small molecule organic materials

DOEpatents

Billinge, Simon; Shankland, Kenneth; Shankland, Norman; Florence, Alastair

2014-06-10

The present invention provides, inter alia, methods of characterizing a small molecule organic material, e.g., a drug or a drug product. This method includes subjecting the solid small molecule organic material to x-ray total scattering analysis at a short wavelength, collecting data generated thereby, and mathematically transforming the data to provide a refined set of data.

Group specific internal standard technology (GSIST) for simultaneous identification and quantification of small molecules

DOEpatents

Adamec, Jiri; Yang, Wen-Chu; Regnier, Fred E

2014-01-14

Reagents and methods are provided that permit simultaneous analysis of multiple diverse small molecule analytes present in a complex mixture. Samples are labeled with chemically identical but isotopically distince forms of the labeling reagent, and analyzed using mass spectrometry. A single reagent simultaneously derivatizes multiple small molecule analytes having different reactive functional groups.

Crossing borders to bind proteins--a new concept in protein recognition based on the conjugation of small organic molecules or short peptides to polypeptides from a designed set.

PubMed

Baltzer, Lars

2011-06-01

A new concept for protein recognition and binding is highlighted. The conjugation of small organic molecules or short peptides to polypeptides from a designed set provides binder molecules that bind proteins with high affinities, and with selectivities that are equal to those of antibodies. The small organic molecules or peptides need to bind the protein targets but only with modest affinities and selectivities, because conjugation to the polypeptides results in molecules with dramatically improved binder performance. The polypeptides are selected from a set of only sixteen sequences designed to bind, in principle, any protein. The small number of polypeptides used to prepare high-affinity binders contrasts sharply with the huge libraries used in binder technologies based on selection or immunization. Also, unlike antibodies and engineered proteins, the polypeptides have unordered three-dimensional structures and adapt to the proteins to which they bind. Binder molecules for the C-reactive protein, human carbonic anhydrase II, acetylcholine esterase, thymidine kinase 1, phosphorylated proteins, the D-dimer, and a number of antibodies are used as examples to demonstrate that affinities are achieved that are higher than those of the small molecules or peptides by as much as four orders of magnitude. Evaluation by pull-down experiments and ELISA-based tests in human serum show selectivities to be equal to those of antibodies. Small organic molecules and peptides are readily available from pools of endogenous ligands, enzyme substrates, inhibitors or products, from screened small molecule libraries, from phage display, and from mRNA display. The technology is an alternative to established binder concepts for applications in drug development, diagnostics, medical imaging, and protein separation.

Membrane Fusion Induced by Small Molecules and Ions

PubMed Central

Mondal Roy, Sutapa; Sarkar, Munna

2011-01-01

Membrane fusion is a key event in many biological processes. These processes are controlled by various fusogenic agents of which proteins and peptides from the principal group. The fusion process is characterized by three major steps, namely, inter membrane contact, lipid mixing forming the intermediate step, pore opening and finally mixing of inner contents of the cells/vesicles. These steps are governed by energy barriers, which need to be overcome to complete fusion. Structural reorganization of big molecules like proteins/peptides, supplies the required driving force to overcome the energy barrier of the different intermediate steps. Small molecules/ions do not share this advantage. Hence fusion induced by small molecules/ions is expected to be different from that induced by proteins/peptides. Although several reviews exist on membrane fusion, no recent review is devoted solely to small moleculs/ions induced membrane fusion. Here we intend to present, how a variety of small molecules/ions act as independent fusogens. The detailed mechanism of some are well understood but for many it is still an unanswered question. Clearer understanding of how a particular small molecule can control fusion will open up a vista to use these moleucles instead of proteins/peptides to induce fusion both in vivo and in vitro fusion processes. PMID:21660306

Perylene-Diimide Based Donor-Acceptor-Donor Type Small-Molecule Acceptors for Solution-Processable Organic Solar Cells

NASA Astrophysics Data System (ADS)

Ganesamoorthy, Ramasamy; Vijayaraghavan, Rajagopalan; Sakthivel, Pachagounder

2017-12-01

Development of nonfullerene acceptors plays an important role in the commercial availability of plastic solar cells. We report herein synthesis of bay-substituted donor-acceptor-donor (D-A-D)-type perylene diimide (PDI)-based small molecules (SM-1 to SM-4) by Suzuki coupling method and their use as acceptors in bulk heterojunction organic solar cells (BHJ-OSCs) with poly(3-hexylthiophene) (P3HT) polymer donor. We varied the number of electron-rich thiophene units and the solubilizing side chains and also evaluated the optical and electrochemical properties of the small molecules. The synthesized small molecules were confirmed by Fourier-transform infrared (FT-IR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, and high-resolution mass spectroscopy (HR-MS). The small molecules showed extensive and strong absorption in the ultraviolet-visible (UV-Vis) region up to 750 nm, with bandgap (E_{{g}}^{{opt}} ) reduced below <2 eV. The energy levels of small molecules SM-1 to SM-4 were suitable for use as electron-accepting materials. The small molecules showed good thermal stability up to 300°C. BHJ-OSCs with SM-1 and P3HT polymer donor showed maximum power conversion efficiency (PCE) of 0.19% with V oc of 0.30 V, J sc of 1.72 mA cm-2, and fill factor (FF) of 37%. The PCE decreased with the number of thiophene units. The PCE of SM-2 was lower than that of SM-1. This difference in PCE can be explained by the higher aggregation tendency of the bithiophene compared with the thiophene unit. Introduction of the solubilizing group in the bay position increased the aggregation property, leading to much lower PCE than for the small molecules without solubilizing group.

Hierarchical virtual screening approaches in small molecule drug discovery.

PubMed

Kumar, Ashutosh; Zhang, Kam Y J

2015-01-01

Virtual screening has played a significant role in the discovery of small molecule inhibitors of therapeutic targets in last two decades. Various ligand and structure-based virtual screening approaches are employed to identify small molecule ligands for proteins of interest. These approaches are often combined in either hierarchical or parallel manner to take advantage of the strength and avoid the limitations associated with individual methods. Hierarchical combination of ligand and structure-based virtual screening approaches has received noteworthy success in numerous drug discovery campaigns. In hierarchical virtual screening, several filters using ligand and structure-based approaches are sequentially applied to reduce a large screening library to a number small enough for experimental testing. In this review, we focus on different hierarchical virtual screening strategies and their application in the discovery of small molecule modulators of important drug targets. Several virtual screening studies are discussed to demonstrate the successful application of hierarchical virtual screening in small molecule drug discovery. Copyright © 2014 Elsevier Inc. All rights reserved.

Systematic development of small molecules to inhibit specific microscopic steps of Aβ42 aggregation in Alzheimer's disease.

PubMed

Habchi, Johnny; Chia, Sean; Limbocker, Ryan; Mannini, Benedetta; Ahn, Minkoo; Perni, Michele; Hansson, Oskar; Arosio, Paolo; Kumita, Janet R; Challa, Pavan Kumar; Cohen, Samuel I A; Linse, Sara; Dobson, Christopher M; Knowles, Tuomas P J; Vendruscolo, Michele

2017-01-10

The aggregation of the 42-residue form of the amyloid-β peptide (Aβ42) is a pivotal event in Alzheimer's disease (AD). The use of chemical kinetics has recently enabled highly accurate quantifications of the effects of small molecules on specific microscopic steps in Aβ42 aggregation. Here, we exploit this approach to develop a rational drug discovery strategy against Aβ42 aggregation that uses as a read-out the changes in the nucleation and elongation rate constants caused by candidate small molecules. We thus identify a pool of compounds that target specific microscopic steps in Aβ42 aggregation. We then test further these small molecules in human cerebrospinal fluid and in a Caenorhabditis elegans model of AD. Our results show that this strategy represents a powerful approach to identify systematically small molecule lead compounds, thus offering an appealing opportunity to reduce the attrition problem in drug discovery.

Synthesis of many different types of organic small molecules using one automated process.

PubMed

Li, Junqi; Ballmer, Steven G; Gillis, Eric P; Fujii, Seiko; Schmidt, Michael J; Palazzolo, Andrea M E; Lehmann, Jonathan W; Morehouse, Greg F; Burke, Martin D

2015-03-13

Small-molecule synthesis usually relies on procedures that are highly customized for each target. A broadly applicable automated process could greatly increase the accessibility of this class of compounds to enable investigations of their practical potential. Here we report the synthesis of 14 distinct classes of small molecules using the same fully automated process. This was achieved by strategically expanding the scope of a building block-based synthesis platform to include even C(sp3)-rich polycyclic natural product frameworks and discovering a catch-and-release chromatographic purification protocol applicable to all of the corresponding intermediates. With thousands of compatible building blocks already commercially available, many small molecules are now accessible with this platform. More broadly, these findings illuminate an actionable roadmap to a more general and automated approach for small-molecule synthesis. Copyright © 2015, American Association for the Advancement of Science.

Antibody-Mediated Small Molecule Detection Using Programmable DNA-Switches.

PubMed

Rossetti, Marianna; Ippodrino, Rudy; Marini, Bruna; Palleschi, Giuseppe; Porchetta, Alessandro

2018-06-13

The development of rapid, cost-effective, and single-step methods for the detection of small molecules is crucial for improving the quality and efficiency of many applications ranging from life science to environmental analysis. Unfortunately, current methodologies still require multiple complex, time-consuming washing and incubation steps, which limit their applicability. In this work we present a competitive DNA-based platform that makes use of both programmable DNA-switches and antibodies to detect small target molecules. The strategy exploits both the advantages of proximity-based methods and structure-switching DNA-probes. The platform is modular and versatile and it can potentially be applied for the detection of any small target molecule that can be conjugated to a nucleic acid sequence. Here the rational design of programmable DNA-switches is discussed, and the sensitive, rapid, and single-step detection of different environmentally relevant small target molecules is demonstrated.

Large scale nanoparticle screening for small molecule analysis in laser desorption ionization mass spectrometry

DOE PAGES

Yagnik, Gargey B.; Hansen, Rebecca L.; Korte, Andrew R.; ...

2016-08-30

Nanoparticles (NPs) have been suggested as efficient matrixes for small molecule profiling and imaging by laser-desorption ionization mass spectrometry (LDI-MS), but so far there has been no systematic study comparing different NPs in the analysis of various classes of small molecules. Here, we present a large scale screening of 13 NPs for the analysis of two dozen small metabolite molecules. Many NPs showed much higher LDI efficiency than organic matrixes in positive mode and some NPs showed comparable efficiencies for selected analytes in negative mode. Our results suggest that a thermally driven desorption process is a key factor for metalmore » oxide NPs, but chemical interactions are also very important, especially for other NPs. Furthermore, the screening results provide a useful guideline for the selection of NPs in the LDI-MS analysis of small molecules.« less

Large scale nanoparticle screening for small molecule analysis in laser desorption ionization mass spectrometry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yagnik, Gargey B.; Hansen, Rebecca L.; Korte, Andrew R.

Nanoparticles (NPs) have been suggested as efficient matrixes for small molecule profiling and imaging by laser-desorption ionization mass spectrometry (LDI-MS), but so far there has been no systematic study comparing different NPs in the analysis of various classes of small molecules. Here, we present a large scale screening of 13 NPs for the analysis of two dozen small metabolite molecules. Many NPs showed much higher LDI efficiency than organic matrixes in positive mode and some NPs showed comparable efficiencies for selected analytes in negative mode. Our results suggest that a thermally driven desorption process is a key factor for metalmore » oxide NPs, but chemical interactions are also very important, especially for other NPs. Furthermore, the screening results provide a useful guideline for the selection of NPs in the LDI-MS analysis of small molecules.« less

Small Molecule Signaling Agents: The Integrated Chemistry and Biochemistry of Nitrogen Oxides, Oxides of Carbon, Dioxygen, Hydrogen Sulfide, and Their Derived Species

PubMed Central

Fukuto, Jon M.; Carrington, Samantha J.; Tantillo, Dean J.; Harrison, Jason G.; Ignarro, Louis J.; Freeman, Bruce A.; Chen, Andrew; Wink, David A.

2014-01-01

Several small molecule species formally known primarily as toxic gases have, over the past 20 years, been shown to be endogenously generated signaling molecules. The biological signaling associated with the small molecules NO, CO, H2S (and the nonendogenously generated O2), and their derived species have become a topic of extreme interest. It has become increasingly clear that these small molecule signaling agents form an integrated signaling web that affects/regulates numerous physiological processes. The chemical interactions between these species and each other or biological targets is an important factor in their roles as signaling agents. Thus, a fundamental understanding of the chemistry of these molecules is essential to understanding their biological/physiological utility. This review focuses on this chemistry and attempts to establish the chemical basis for their signaling functions. PMID:22263838

Fluorination-enabled optimal morphology leads to over 11% efficiency for inverted small-molecule organic solar cells

PubMed Central

Deng, Dan; Zhang, Yajie; Zhang, Jianqi; Wang, Zaiyu; Zhu, Lingyun; Fang, Jin; Xia, Benzheng; Wang, Zhen; Lu, Kun; Ma, Wei; Wei, Zhixiang

2016-01-01

Solution-processable small molecules for organic solar cells have attracted intense attention for their advantages of definite molecular structures compared with their polymer counterparts. However, the device efficiencies based on small molecules are still lower than those of polymers, especially for inverted devices, the highest efficiency of which is <9%. Here we report three novel solution-processable small molecules, which contain π-bridges with gradient-decreased electron density and end acceptors substituted with various fluorine atoms (0F, 1F and 2F, respectively). Fluorination leads to an optimal active layer morphology, including an enhanced domain purity, the formation of hierarchical domain size and a directional vertical phase gradation. The optimal morphology balances charge separation and transfer, and facilitates charge collection. As a consequence, fluorinated molecules exhibit excellent inverted device performance, and an average power conversion efficiency of 11.08% is achieved for a two-fluorine atom substituted molecule. PMID:27991486

Detection of ultratrace phosphorus and sulfur by quadrupole ICPMS with dynamic reaction cell.

PubMed

Bandura, Dmitry R; Baranov, Vladimir I; Tanner, Scott D

2002-04-01

A method of detection of ultratrace phosphorus and sulfur that uses reaction with O2 in a dynamic reaction cell (DRC) to oxidize S+ and P+ to allow their detection as SO+ and PO+ is described. The method reduces the effect of polyatomic isobaric interferences at m/z = 31 and 32 by detecting P+ and S+ as the product oxide ions that are less interfered. Use of an axial field in the DRC improves transmission of the product oxide ions 4-6 times. With no axial field, detection limits (3sigma, 5-s integration) of 0.20 and 0.52 ng/mL, with background equivalent concentrations of 0.53 and 4.8 ng/mL, respectively, are achieved. At an optimum axial field potential (200 V), the detection limits are 0.06 ng/mL for P and 0.2 ng/mL for S, respectively. The method is used for determining the degree of phosphorylation of beta-casein, and regular and dephosphorylated alpha-caseins at 10-1000 fmol/microL concentration, with 5-10% v/v organic sample matrix (acetonitrile, formic acid, ammonium bicarbonate). The measured degree of phosphorylation for beta-casein (4.9 phosphorus atoms/molecule) and regular alpha-casein (8.8 phoshorus atoms/molecule) are in good agreement with the structural data for the proteins. The P/S ratio for regular alpha-casein (1.58) is in good agreement with the ratio of the number of phosphorylation sites to the number of sulfur-containing amino acid residues cysteine and methionine. The P/S ratio for commercially available dephosphorylated alpha-casein is measured at 0.41 (approximately 26% residual phosphate).

Diatomics-in-molecules description of the Rg-Hal2 rare gas-halogen van der Waals complexes with applications to He-Cl2

NASA Astrophysics Data System (ADS)

Grigorenko, B. L.; Nemukhin, A. V.; Buchachenko, A. A.; Stepanov, N. F.; Umanskii, S. Ya.

1997-03-01

The diatomics-in-molecules (DIM) technique is applied for a description of the low-lying states of the Rg-Hal2 van der Waals complexes correlating with the lowest states of constituent atoms Rg(1S)+Hal(2Pj)+Hal(2Pj). The important feature of this approach is the construction of polyatomic basis functions as products of the Hal2 diatomic eigenstates classified within the Hund "c" scheme and the atomic rare gas wave function. Necessary transformations to the other basis set representations are described, and finally all the matrix elements are expressed in terms of nonrelativistic adiabatic energies of Hal2 and Rg Hal fragments and spin-orbit splitting constant of the halogen atom. Our main concern is to test the DIM-based approximations of different levels taking the He-Cl2 system as an example. Namely, we have compared the results obtained within a hierarchy of approaches: (1) the simplest pairwise potential scheme as a far extreme of the DIM model, (2) the same as (1) but with the different components (Σ and Π) for He-Cl interaction, (3) the accurate DIM technique without spin-orbit terms, and (4) the highest level which takes into account all these contributions. The results have been compared to the other DIM like models as well. The shapes of two-dimensional potential surfaces for the ground (X) and excited (B) states of HeCl2, binding energies De with respect to He+Cl2, stretching and bending vibrational frequencies of the complex, binding energies D0, and spectral shifts for the B←X transition are discussed.

[Effect of annealing temperature on the crystallization and spectroscopic response of a small-molecule semiconductor doped in polymer film].

PubMed

Yin, Ming; Zhang, Xin-Ping; Liu, Hong-Mei

2012-11-01

The crystallization properties of the perylene (EPPTC) molecules doped in the solid film of the derivative of polyfluorene (F8BT) at different annealing temperatures, as well as the consequently induced spectroscopic response of the exciplex emission in the heterojunction structures, were studied in the present paper. Experimental results showed that the phase separation between the small and the polymer molecules in the blend film is enhanced with increasing the annealing temperature, which leads to the crystallization of the EPPTC molecules due to the strong pi-pi stacking. The size of the crystal phase increases with increasing the annealing temperature. However, this process weakens the mechanisms of the heterojunction configuration, thus, the total interfacial area between the small and the polymer molecules and the amount of exciplex are reduced significantly in the blend film. Meanwhile, the energy transfer from the polymer to the small molecules is also reduced. As a result, the emission from the exciplex becomes weaker with increasing the annealing temperature, whereas the stronger emission from the polymer molecules and from the crystal phase of the small molecules can be observed. These experimental results are very important for understanding and tailoring the organic heterojunction structures. Furthermore, this provides photophysics for improving the performance of photovoltaic or solar cell devices.

Hippocampal and cortical neuronal growth mediated by the small molecule natural product clovanemagnolol.

PubMed

Khaing, Zin; Kang, Danby; Camelio, Andrew M; Schmidt, Christine E; Siegel, Dionicio

2011-08-15

The use of small molecule surrogates of growth factors that directly or indirectly promote growth represents an attractive approach to regenerative medicine. With synthetic access to clovanemagnolol, a small molecule initially isolated from the bark of the Bigleaf Magnolia tree, we have examined the small molecule's ability to promote growth of embryonic hippocampal and cortical neurons in serum-free medium. Comparisons with magnolol, a known promoter of growth, reveals that clovanmagnolol is a potent neurotrophic agent, promoting neuronal growth at concentrations of 10 nM. In addition, both clovanemagnolol and magnolol promote growth through a biphasic dose response. Copyright © 2011 Elsevier Ltd. All rights reserved.

Second-generation DNA-templated macrocycle libraries for the discovery of bioactive small molecules.

PubMed

Usanov, Dmitry L; Chan, Alix I; Maianti, Juan Pablo; Liu, David R

2018-07-01

DNA-encoded libraries have emerged as a widely used resource for the discovery of bioactive small molecules, and offer substantial advantages compared with conventional small-molecule libraries. Here, we have developed and streamlined multiple fundamental aspects of DNA-encoded and DNA-templated library synthesis methodology, including computational identification and experimental validation of a 20 × 20 × 20 × 80 set of orthogonal codons, chemical and computational tools for enhancing the structural diversity and drug-likeness of library members, a highly efficient polymerase-mediated template library assembly strategy, and library isolation and purification methods. We have integrated these improved methods to produce a second-generation DNA-templated library of 256,000 small-molecule macrocycles with improved drug-like physical properties. In vitro selection of this library for insulin-degrading enzyme affinity resulted in novel insulin-degrading enzyme inhibitors, including one of unusual potency and novel macrocycle stereochemistry (IC 50  = 40 nM). Collectively, these developments enable DNA-templated small-molecule libraries to serve as more powerful, accessible, streamlined and cost-effective tools for bioactive small-molecule discovery.

Use of mRNA expression signatures to discover small molecule inhibitors of skeletal muscle atrophy

PubMed Central

Adams, Christopher M.; Ebert, Scott M.; Dyle, Michael C.

2017-01-01

Purpose of review Here, we discuss a recently developed experimental strategy for discovering small molecules with potential to prevent and treat skeletal muscle atrophy. Recent findings Muscle atrophy involves and requires widespread changes in skeletal muscle gene expression, which generate complex but measurable patterns of positive and negative changes in skeletal muscle mRNA levels (a.k.a. mRNA expression signatures of muscle atrophy). Many bioactive small molecules generate their own characteristic mRNA expression signatures, and by identifying small molecules whose signatures approximate mirror images of muscle atrophy signatures, one may identify small molecules with potential to prevent and/or reverse muscle atrophy. Unlike a conventional drug discovery approach, this strategy does not rely on a predefined molecular target but rather exploits the complexity of muscle atrophy to identify small molecules that counter the entire spectrum of pathological changes in atrophic muscle. We discuss how this strategy has been used to identify two natural compounds, ursolic acid and tomatidine, that reduce muscle atrophy and improve skeletal muscle function. Summary Discovery strategies based on mRNA expression signatures can elucidate new approaches for preserving and restoring muscle mass and function. PMID:25807353

Use of mRNA expression signatures to discover small molecule inhibitors of skeletal muscle atrophy.

PubMed

Adams, Christopher M; Ebert, Scott M; Dyle, Michael C

2015-05-01

Here, we discuss a recently developed experimental strategy for discovering small molecules with potential to prevent and treat skeletal muscle atrophy. Muscle atrophy involves and requires widespread changes in skeletal muscle gene expression, which generate complex but measurable patterns of positive and negative changes in skeletal muscle mRNA levels (a.k.a. mRNA expression signatures of muscle atrophy). Many bioactive small molecules generate their own characteristic mRNA expression signatures, and by identifying small molecules whose signatures approximate mirror images of muscle atrophy signatures, one may identify small molecules with potential to prevent and/or reverse muscle atrophy. Unlike a conventional drug discovery approach, this strategy does not rely on a predefined molecular target but rather exploits the complexity of muscle atrophy to identify small molecules that counter the entire spectrum of pathological changes in atrophic muscle. We discuss how this strategy has been used to identify two natural compounds, ursolic acid and tomatidine, that reduce muscle atrophy and improve skeletal muscle function. Discovery strategies based on mRNA expression signatures can elucidate new approaches for preserving and restoring muscle mass and function.

Mass amplifying probe for sensitive fluorescence anisotropy detection of small molecules in complex biological samples.

PubMed

Cui, Liang; Zou, Yuan; Lin, Ninghang; Zhu, Zhi; Jenkins, Gareth; Yang, Chaoyong James

2012-07-03

Fluorescence anisotropy (FA) is a reliable and excellent choice for fluorescence sensing. One of the key factors influencing the FA value for any molecule is the molar mass of the molecule being measured. As a result, the FA method with functional nucleic acid aptamers has been limited to macromolecules such as proteins and is generally not applicable for the analysis of small molecules because their molecular masses are relatively too small to produce observable FA value changes. We report here a molecular mass amplifying strategy to construct anisotropy aptamer probes for small molecules. The probe is designed in such a way that only when a target molecule binds to the probe does it activate its binding ability to an anisotropy amplifier (a high molecular mass molecule such as protein), thus significantly increasing the molecular mass and FA value of the probe/target complex. Specifically, a mass amplifying probe (MAP) consists of a targeting aptamer domain against a target molecule and molecular mass amplifying aptamer domain for the amplifier protein. The probe is initially rendered inactive by a small blocking strand partially complementary to both target aptamer and amplifier protein aptamer so that the mass amplifying aptamer domain would not bind to the amplifier protein unless the probe has been activated by the target. In this way, we prepared two probes that constitute a target (ATP and cocaine respectively) aptamer, a thrombin (as the mass amplifier) aptamer, and a fluorophore. Both probes worked well against their corresponding small molecule targets, and the detection limits for ATP and cocaine were 0.5 μM and 0.8 μM, respectively. More importantly, because FA is less affected by environmental interferences, ATP in cell media and cocaine in urine were directly detected without any tedious sample pretreatment. Our results established that our molecular mass amplifying strategy can be used to design aptamer probes for rapid, sensitive, and selective detection of small molecules by means of FA in complex biological samples.

Modeling of carbon dioxide condensation in the high pressure flows using the statistical BGK approach

NASA Astrophysics Data System (ADS)

Kumar, Rakesh; Li, Zheng; Levin, Deborah A.

2011-05-01

In this work, we propose a new heat accommodation model to simulate freely expanding homogeneous condensation flows of gaseous carbon dioxide using a new approach, the statistical Bhatnagar-Gross-Krook method. The motivation for the present work comes from the earlier work of Li et al. [J. Phys. Chem. 114, 5276 (2010)] in which condensation models were proposed and used in the direct simulation Monte Carlo method to simulate the flow of carbon dioxide from supersonic expansions of small nozzles into near-vacuum conditions. Simulations conducted for stagnation pressures of one and three bar were compared with the measurements of gas and cluster number densities, cluster size, and carbon dioxide rotational temperature obtained by Ramos et al. [Phys. Rev. A 72, 3204 (2005)]. Due to the high computational cost of direct simulation Monte Carlo method, comparison between simulations and data could only be performed for these stagnation pressures, with good agreement obtained beyond the condensation onset point, in the farfield. As the stagnation pressure increases, the degree of condensation also increases; therefore, to improve the modeling of condensation onset, one must be able to simulate higher stagnation pressures. In simulations of an expanding flow of argon through a nozzle, Kumar et al. [AIAA J. 48, 1531 (2010)] found that the statistical Bhatnagar-Gross-Krook method provides the same accuracy as direct simulation Monte Carlo method, but, at one half of the computational cost. In this work, the statistical Bhatnagar-Gross-Krook method was modified to account for internal degrees of freedom for multi-species polyatomic gases. With the computational approach in hand, we developed and tested a new heat accommodation model for a polyatomic system to properly account for the heat release of condensation. We then developed condensation models in the framework of the statistical Bhatnagar-Gross-Krook method. Simulations were found to agree well with the experiment for all stagnation pressure cases (1-5 bar), validating the accuracy of the Bhatnagar-Gross-Krook based condensation model in capturing the physics of condensation.

Applications of inductively coupled plasma mass spectrometry and laser ablation inductively coupled plasma mass spectrometry in materials science

NASA Astrophysics Data System (ADS)

Becker, Johanna Sabine

2002-12-01

Inductively coupled plasma mass spectrometry (ICP-MS) and laser ablation ICP-MS (LA-ICP-MS) have been applied as the most important inorganic mass spectrometric techniques having multielemental capability for the characterization of solid samples in materials science. ICP-MS is used for the sensitive determination of trace and ultratrace elements in digested solutions of solid samples or of process chemicals (ultrapure water, acids and organic solutions) for the semiconductor industry with detection limits down to sub-picogram per liter levels. Whereas ICP-MS on solid samples (e.g. high-purity ceramics) sometimes requires time-consuming sample preparation for its application in materials science, and the risk of contamination is a serious drawback, a fast, direct determination of trace elements in solid materials without any sample preparation by LA-ICP-MS is possible. The detection limits for the direct analysis of solid samples by LA-ICP-MS have been determined for many elements down to the nanogram per gram range. A deterioration of detection limits was observed for elements where interferences with polyatomic ions occur. The inherent interference problem can often be solved by applying a double-focusing sector field mass spectrometer at higher mass resolution or by collision-induced reactions of polyatomic ions with a collision gas using an ICP-MS fitted with collision cell. The main problem of LA-ICP-MS is quantification if no suitable standard reference materials with a similar matrix composition are available. The calibration problem in LA-ICP-MS can be solved using on-line solution-based calibration, and different procedures, such as external calibration and standard addition, have been discussed with respect to their application in materials science. The application of isotope dilution in solution-based calibration for trace metal determination in small amounts of noble metals has been developed as a new calibration strategy. This review discusses new analytical developments and possible applications of ICP-MS and LA-ICP-MS for the quantitative determination of trace elements and in surface analysis for materials science.

Ion-neutral potential models in atmospheric pressure ion mobility time-of-flight mass spectrometry IM(tof)MS.

PubMed

Steiner, Wes E; English, William A; Hill, Herbert H

2006-02-09

The ion mobilities and their respective masses of several classes of amines (primary, secondary, and tertiary) were measured by electrospray ionization atmospheric pressure ion mobility time-of-flight mass spectrometry IM(tof)MS. The experimental data obtained were comparatively analyzed by the one-temperature kinetic theory of Chapman-Enskog. Several theoretical models were used to estimate the collision cross-sections; they include the rigid-sphere, polarization-limit, 12-6-4, and 12-4 potential models. These models were investigated to represent the interaction potentials contained within the collision integral that occurs between the polyatomic ions and the neutral drift gas molecules. The effectiveness of these collision cross-section models on predicting the mobility of these amine ions was explored. Moreover, the effects of drift gas selectivity on the reduced-mass term and in the collision cross-section term was examined. Use of a series of drift gases, namely, helium, neon, argon, nitrogen, and carbon dioxide, made it possible to distinguish between mass effects and polarizability effects. It was found that the modified 12-4 potential that compensates for the center of charge not being at the same location as the centers of mass showed improved agreement over the other collision cross-section models with respect to experimental data.

Consistent post-reaction vibrational energy redistribution in DSMC simulations using TCE model

NASA Astrophysics Data System (ADS)

Borges Sebastião, Israel; Alexeenko, Alina

2016-10-01

The direct simulation Monte Carlo (DSMC) method has been widely applied to study shockwaves, hypersonic reentry flows, and other nonequilibrium flow phenomena. Although there is currently active research on high-fidelity models based on ab initio data, the total collision energy (TCE) and Larsen-Borgnakke (LB) models remain the most often used chemistry and relaxation models in DSMC simulations, respectively. The conventional implementation of the discrete LB model, however, may not satisfy detailed balance when recombination and exchange reactions play an important role in the flow energy balance. This issue can become even more critical in reacting mixtures involving polyatomic molecules, such as in combustion. In this work, this important shortcoming is addressed and an empirical approach to consistently specify the post-reaction vibrational states close to thermochemical equilibrium conditions is proposed within the TCE framework. Following Bird's quantum-kinetic (QK) methodology for populating post-reaction states, the new TCE-based approach involves two main steps. The state-specific TCE reaction probabilities for a forward reaction are first pre-computed from equilibrium 0-D simulations. These probabilities are then employed to populate the post-reaction vibrational states of the corresponding reverse reaction. The new approach is illustrated by application to exchange and recombination reactions relevant to H2-O2 combustion processes.

Influence of thermocleavable functionality on organic field-effect transistor performance of small molecules

NASA Astrophysics Data System (ADS)

Mahale, Rajashree Y.; Dharmapurikar, Satej S.; Chini, Mrinmoy Kumar; Venugopalan, Vijay

2017-06-01

Diketopyrrolopyrrole based donor-acceptor-donor conjugated small molecules using ethylene dioxythiophene as a donor was synthesized. Electron deficient diketopyrrolopyrrole unit was substituted with thermocleavable (tert-butyl acetate) side chains. The thermal treatment of the molecules at 160 °C eliminated the tert-butyl ester group results in the formation of corresponding acid. Optical and theoretical studies revealed that the molecules adopted a change in molecular arrangement after thermolysis. The conjugated small molecules possessed p-channel charge transport characteristics in organic field effect transistors. The charge carrier mobility was increased after thermolysis of tert-butyl ester group to 5.07 × 10-5 cm2/V s.

Discovery of Small Molecules that Inhibit the Disordered Protein, p27Kip1

PubMed Central

Iconaru, Luigi I.; Ban, David; Bharatham, Kavitha; Ramanathan, Arvind; Zhang, Weixing; Shelat, Anang A.; Zuo, Jian; Kriwacki, Richard W.

2015-01-01

Disordered proteins are highly prevalent in biological systems, they control myriad signaling and regulatory processes, and their levels and/or cellular localization are often altered in human disease. In contrast to folded proteins, disordered proteins, due to conformational heterogeneity and dynamics, are not considered viable drug targets. We challenged this paradigm by identifying through NMR-based screening small molecules that bound specifically, albeit weakly, to the disordered cell cycle regulator, p27Kip1 (p27). Two groups of molecules bound to sites created by transient clusters of aromatic residues within p27. Conserved chemical features within these two groups of small molecules exhibited complementarity to their binding sites within p27, establishing structure-activity relationships for small molecule:disordered protein interactions. Finally, one compound counteracted the Cdk2/cyclin A inhibitory function of p27 in vitro, providing proof-of-principle that small molecules can inhibit the function of a disordered protein (p27) through sequestration in a conformation incapable of folding and binding to a natural regulatory target (Cdk2/cyclin A). PMID:26507530

Discovery of Small Molecules that Inhibit the Disordered Protein, p27 Kip1

DOE PAGES

Iconaru, Luigi I.; Ban, David; Bharatham, Kavitha; ...

2015-10-28

In disordered proteins we see that they are highly prevalent in biological systems. They control myriad signaling and regulatory processes, and their levels and/or cellular localization are often altered in human disease. In contrast to folded proteins, disordered proteins, due to conformational heterogeneity and dynamics, are not considered viable drug targets. We challenged this paradigm by identifying through NMR-based screening small molecules that bound specifically, albeit weakly, to the disordered cell cycle regulator, p27 Kip1 (p27). Moreover, two groups of molecules bound to sites created by transient clusters of aromatic residues within p27. Conserved chemical features within these two groupsmore » of small molecules exhibited complementarity to their binding sites within p27, establishing structure-activity relationships for small molecule: disordered protein interactions. Finally, one compound counteracted the Cdk2/cyclin A inhibitory function of p27 in vitro, providing proof-of- principle that small molecules can inhibit the function of a disordered protein (p27) through sequestration in a conformation incapable of folding and binding to a natural regulatory target (Cdk2/cyclin A).« less

Strategy to discover diverse optimal molecules in the small molecule universe.

PubMed

Rupakheti, Chetan; Virshup, Aaron; Yang, Weitao; Beratan, David N

2015-03-23

The small molecule universe (SMU) is defined as a set of over 10(60) synthetically feasible organic molecules with molecular weight less than ∼500 Da. Exhaustive enumerations and evaluation of all SMU molecules for the purpose of discovering favorable structures is impossible. We take a stochastic approach and extend the ACSESS framework ( Virshup et al. J. Am. Chem. Soc. 2013 , 135 , 7296 - 7303 ) to develop diversity oriented molecular libraries that can generate a set of compounds that is representative of the small molecule universe and that also biases the library toward favorable physical property values. We show that the approach is efficient compared to exhaustive enumeration and to existing evolutionary algorithms for generating such libraries by testing in the NKp fitness landscape model and in the fully enumerated GDB-9 chemical universe containing 3 × 10(5) molecules.

Strategy To Discover Diverse Optimal Molecules in the Small Molecule Universe

PubMed Central

2015-01-01

The small molecule universe (SMU) is defined as a set of over 1060 synthetically feasible organic molecules with molecular weight less than ∼500 Da. Exhaustive enumerations and evaluation of all SMU molecules for the purpose of discovering favorable structures is impossible. We take a stochastic approach and extend the ACSESS framework (Virshup et al. J. Am. Chem. Soc.2013, 135, 7296–730323548177) to develop diversity oriented molecular libraries that can generate a set of compounds that is representative of the small molecule universe and that also biases the library toward favorable physical property values. We show that the approach is efficient compared to exhaustive enumeration and to existing evolutionary algorithms for generating such libraries by testing in the NKp fitness landscape model and in the fully enumerated GDB-9 chemical universe containing 3 × 105 molecules. PMID:25594586

Construction of Ligand Group Orbitals for Polyatomics and Transition-Metal Complexes Using an Intuitive Symmetry-Based Approach

ERIC Educational Resources Information Center

Johnson, Adam R.

2013-01-01

A molecular orbital (MO) diagram, especially its frontier orbitals, explains the bonding and reactivity for a chemical compound. It is therefore important for students to learn how to construct one. The traditional methods used to derive these diagrams rely on linear algebra techniques to combine ligand orbitals into symmetry-adapted linear…

Prediction of small molecule binding property of protein domains with Bayesian classifiers based on Markov chains.

PubMed

Bulashevska, Alla; Stein, Martin; Jackson, David; Eils, Roland

2009-12-01

Accurate computational methods that can help to predict biological function of a protein from its sequence are of great interest to research biologists and pharmaceutical companies. One approach to assume the function of proteins is to predict the interactions between proteins and other molecules. In this work, we propose a machine learning method that uses a primary sequence of a domain to predict its propensity for interaction with small molecules. By curating the Pfam database with respect to the small molecule binding ability of its component domains, we have constructed a dataset of small molecule binding and non-binding domains. This dataset was then used as training set to learn a Bayesian classifier, which should distinguish members of each class. The domain sequences of both classes are modelled with Markov chains. In a Jack-knife test, our classification procedure achieved the predictive accuracies of 77.2% and 66.7% for binding and non-binding classes respectively. We demonstrate the applicability of our classifier by using it to identify previously unknown small molecule binding domains. Our predictions are available as supplementary material and can provide very useful information to drug discovery specialists. Given the ubiquitous and essential role small molecules play in biological processes, our method is important for identifying pharmaceutically relevant components of complete proteomes. The software is available from the author upon request.

Small Molecule Protection of Bone Marrow Hematopoietic Stem Cells

DTIC Science & Technology

2015-10-01

several recently identified small molecules can protect hematopoietic stem cells (HSCs) from damage or killing by endogenous aldehydes . Proof-of-concept...anemia bone marrow failure CD34+ hematopoietic stem cells aldehydes formaldehyde DNA damage DNA base adduct DNA-protein crosslink mass...below. Revised Specific Aim 1: Small molecule protection of human cells from aldehyde - induced killing (in vitro studies - no mice or human subjects

DG-AMMOS: a new tool to generate 3d conformation of small molecules using distance geometry and automated molecular mechanics optimization for in silico screening.

PubMed

Lagorce, David; Pencheva, Tania; Villoutreix, Bruno O; Miteva, Maria A

2009-11-13

Discovery of new bioactive molecules that could enter drug discovery programs or that could serve as chemical probes is a very complex and costly endeavor. Structure-based and ligand-based in silico screening approaches are nowadays extensively used to complement experimental screening approaches in order to increase the effectiveness of the process and facilitating the screening of thousands or millions of small molecules against a biomolecular target. Both in silico screening methods require as input a suitable chemical compound collection and most often the 3D structure of the small molecules has to be generated since compounds are usually delivered in 1D SMILES, CANSMILES or in 2D SDF formats. Here, we describe the new open source program DG-AMMOS which allows the generation of the 3D conformation of small molecules using Distance Geometry and their energy minimization via Automated Molecular Mechanics Optimization. The program is validated on the Astex dataset, the ChemBridge Diversity database and on a number of small molecules with known crystal structures extracted from the Cambridge Structural Database. A comparison with the free program Balloon and the well-known commercial program Omega generating the 3D of small molecules is carried out. The results show that the new free program DG-AMMOS is a very efficient 3D structure generator engine. DG-AMMOS provides fast, automated and reliable access to the generation of 3D conformation of small molecules and facilitates the preparation of a compound collection prior to high-throughput virtual screening computations. The validation of DG-AMMOS on several different datasets proves that generated structures are generally of equal quality or sometimes better than structures obtained by other tested methods.

Cheminformatics-aided discovery of small-molecule Protein-Protein Interaction (PPI) dual inhibitors of Tumor Necrosis Factor (TNF) and Receptor Activator of NF-κB Ligand (RANKL).

PubMed

Melagraki, Georgia; Ntougkos, Evangelos; Rinotas, Vagelis; Papaneophytou, Christos; Leonis, Georgios; Mavromoustakos, Thomas; Kontopidis, George; Douni, Eleni; Afantitis, Antreas; Kollias, George

2017-04-01

We present an in silico drug discovery pipeline developed and applied for the identification and virtual screening of small-molecule Protein-Protein Interaction (PPI) compounds that act as dual inhibitors of TNF and RANKL through the trimerization interface. The cheminformatics part of the pipeline was developed by combining structure-based with ligand-based modeling using the largest available set of known TNF inhibitors in the literature (2481 small molecules). To facilitate virtual screening, the consensus predictive model was made freely available at: http://enalos.insilicotox.com/TNFPubChem/. We thus generated a priority list of nine small molecules as candidates for direct TNF function inhibition. In vitro evaluation of these compounds led to the selection of two small molecules that act as potent direct inhibitors of TNF function, with IC50 values comparable to those of a previously-described direct inhibitor (SPD304), but with significantly reduced toxicity. These molecules were also identified as RANKL inhibitors and validated in vitro with respect to this second functionality. Direct binding of the two compounds was confirmed both for TNF and RANKL, as well as their ability to inhibit the biologically-active trimer forms. Molecular dynamics calculations were also carried out for the two small molecules in each protein to offer additional insight into the interactions that govern TNF and RANKL complex formation. To our knowledge, these compounds, namely T8 and T23, constitute the second and third published examples of dual small-molecule direct function inhibitors of TNF and RANKL, and could serve as lead compounds for the development of novel treatments for inflammatory and autoimmune diseases.

Profiling protein function with small molecule microarrays

PubMed Central

Winssinger, Nicolas; Ficarro, Scott; Schultz, Peter G.; Harris, Jennifer L.

2002-01-01

The regulation of protein function through posttranslational modification, local environment, and protein–protein interaction is critical to cellular function. The ability to analyze on a genome-wide scale protein functional activity rather than changes in protein abundance or structure would provide important new insights into complex biological processes. Herein, we report the application of a spatially addressable small molecule microarray to an activity-based profile of proteases in crude cell lysates. The potential of this small molecule-based profiling technology is demonstrated by the detection of caspase activation upon induction of apoptosis, characterization of the activated caspase, and inhibition of the caspase-executed apoptotic phenotype using the small molecule inhibitor identified in the microarray-based profile. PMID:12167675

Free-standing few-layered graphene oxide films: selective, steady and lasting permeation of organic molecules with adjustable speeds

NASA Astrophysics Data System (ADS)

Huang, Tao; An, Qi; Luan, Xinglong; Zhang, Qian; Zhang, Yihe

2016-01-01

A variety of small molecules with diameters around 1 nm possess a range of functions, such as antibiotic, antimicrobic, anticoagulant, pesticidal and chemotherapy effects, making these molecules especially useful in various applications ranging from medical treatment to environmental microbiological control. However, the long-term steady delivery (release or permeation) of these small molecules with adjustable and controllable speeds has remained an especially challenging task. In this study, we prepared covalently cross-linked free-standing few-layered GO films using a layer-by-layer technique in combination with photochemical cross-linkages, and achieved a controlled release of positively charged, negatively charged, and zwitterionic small molecules with adjustable and controllable speeds. The steady delivery of the small molecule lasted up to 9 days. Other functionalities, such as graphene-enhanced Raman spectra and electrochemical properties that could also be integrated or employed in delivery systems, were also studied for our films. We expect the special molecular delivery properties of our films to lead to new possibilities in drug/fertilizer delivery and environmental microbiological control applications.A variety of small molecules with diameters around 1 nm possess a range of functions, such as antibiotic, antimicrobic, anticoagulant, pesticidal and chemotherapy effects, making these molecules especially useful in various applications ranging from medical treatment to environmental microbiological control. However, the long-term steady delivery (release or permeation) of these small molecules with adjustable and controllable speeds has remained an especially challenging task. In this study, we prepared covalently cross-linked free-standing few-layered GO films using a layer-by-layer technique in combination with photochemical cross-linkages, and achieved a controlled release of positively charged, negatively charged, and zwitterionic small molecules with adjustable and controllable speeds. The steady delivery of the small molecule lasted up to 9 days. Other functionalities, such as graphene-enhanced Raman spectra and electrochemical properties that could also be integrated or employed in delivery systems, were also studied for our films. We expect the special molecular delivery properties of our films to lead to new possibilities in drug/fertilizer delivery and environmental microbiological control applications. Electronic supplementary information (ESI) available: AFM images of GO and GO films, UV-vis spectra of delayed release, and permeation fidelities. See DOI: 10.1039/c5nr08129g

A Fragment-Based Method of Creating Small-Molecule Libraries to Target the Aggregation of Intrinsically Disordered Proteins.

PubMed

Joshi, Priyanka; Chia, Sean; Habchi, Johnny; Knowles, Tuomas P J; Dobson, Christopher M; Vendruscolo, Michele

2016-03-14

The aggregation process of intrinsically disordered proteins (IDPs) has been associated with a wide range of neurodegenerative disorders, including Alzheimer's and Parkinson's diseases. Currently, however, no drug in clinical use targets IDP aggregation. To facilitate drug discovery programs in this important and challenging area, we describe a fragment-based approach of generating small-molecule libraries that target specific IDPs. The method is based on the use of molecular fragments extracted from compounds reported in the literature to inhibit of the aggregation of IDPs. These fragments are used to screen existing large generic libraries of small molecules to form smaller libraries specific for given IDPs. We illustrate this approach by describing three distinct small-molecule libraries to target, Aβ, tau, and α-synuclein, which are three IDPs implicated in Alzheimer's and Parkinson's diseases. The strategy described here offers novel opportunities for the identification of effective molecular scaffolds for drug discovery for neurodegenerative disorders and to provide insights into the mechanism of small-molecule binding to IDPs.

Systematic development of small molecules to inhibit specific microscopic steps of Aβ42 aggregation in Alzheimer’s disease

PubMed Central

Habchi, Johnny; Chia, Sean; Limbocker, Ryan; Mannini, Benedetta; Ahn, Minkoo; Perni, Michele; Hansson, Oskar; Arosio, Paolo; Kumita, Janet R.; Challa, Pavan Kumar; Cohen, Samuel I. A.; Dobson, Christopher M.; Knowles, Tuomas P. J.; Vendruscolo, Michele

2017-01-01

The aggregation of the 42-residue form of the amyloid-β peptide (Aβ42) is a pivotal event in Alzheimer’s disease (AD). The use of chemical kinetics has recently enabled highly accurate quantifications of the effects of small molecules on specific microscopic steps in Aβ42 aggregation. Here, we exploit this approach to develop a rational drug discovery strategy against Aβ42 aggregation that uses as a read-out the changes in the nucleation and elongation rate constants caused by candidate small molecules. We thus identify a pool of compounds that target specific microscopic steps in Aβ42 aggregation. We then test further these small molecules in human cerebrospinal fluid and in a Caenorhabditis elegans model of AD. Our results show that this strategy represents a powerful approach to identify systematically small molecule lead compounds, thus offering an appealing opportunity to reduce the attrition problem in drug discovery. PMID:28011763

Genome-Scale Architecture of Small Molecule Regulatory Networks and the Fundamental Trade-Off between Regulation and Enzymatic Activity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reznik, Ed; Christodoulou, Dimitris; Goldford, Joshua E.

Metabolic flux is in part regulated by endogenous small molecules that modulate the catalytic activity of an enzyme, e.g., allosteric inhibition. In contrast to transcriptional regulation of enzymes, technical limitations have hindered the production of a genome-scale atlas of small molecule-enzyme regulatory interactions. Here, we develop a framework leveraging the vast, but fragmented, biochemical literature to reconstruct and analyze the small molecule regulatory network (SMRN) of the model organism Escherichia coli, including the primary metabolite regulators and enzyme targets. Using metabolic control analysis, we prove a fundamental trade-off between regulation and enzymatic activity, and we combine it with metabolomic measurementsmore » and the SMRN to make inferences on the sensitivity of enzymes to their regulators. By generalizing the analysis to other organisms, we identify highly conserved regulatory interactions across evolutionarily divergent species, further emphasizing a critical role for small molecule interactions in the maintenance of metabolic homeostasis.« less

Simultaneous optimization of biomolecular energy function on features from small molecules and macromolecules

PubMed Central

Park, Hahnbeom; Bradley, Philip; Greisen, Per; Liu, Yuan; Mulligan, Vikram Khipple; Kim, David E.; Baker, David; DiMaio, Frank

2017-01-01

Most biomolecular modeling energy functions for structure prediction, sequence design, and molecular docking, have been parameterized using existing macromolecular structural data; this contrasts molecular mechanics force fields which are largely optimized using small-molecule data. In this study, we describe an integrated method that enables optimization of a biomolecular modeling energy function simultaneously against small-molecule thermodynamic data and high-resolution macromolecular structural data. We use this approach to develop a next-generation Rosetta energy function that utilizes a new anisotropic implicit solvation model, and an improved electrostatics and Lennard-Jones model, illustrating how energy functions can be considerably improved in their ability to describe large-scale energy landscapes by incorporating both small-molecule and macromolecule data. The energy function improves performance in a wide range of protein structure prediction challenges, including monomeric structure prediction, protein-protein and protein-ligand docking, protein sequence design, and prediction of the free energy changes by mutation, while reasonably recapitulating small-molecule thermodynamic properties. PMID:27766851

Identifying the preferred RNA motifs and chemotypes that interact by probing millions of combinations.

PubMed

Tran, Tuan; Disney, Matthew D

2012-01-01

RNA is an important therapeutic target but information about RNA-ligand interactions is limited. Here, we report a screening method that probes over 3,000,000 combinations of RNA motif-small molecule interactions to identify the privileged RNA structures and chemical spaces that interact. Specifically, a small molecule library biased for binding RNA was probed for binding to over 70,000 unique RNA motifs in a high throughput solution-based screen. The RNA motifs that specifically bind each small molecule were identified by microarray-based selection. In this library-versus-library or multidimensional combinatorial screening approach, hairpin loops (among a variety of RNA motifs) were the preferred RNA motif space that binds small molecules. Furthermore, it was shown that indole, 2-phenyl indole, 2-phenyl benzimidazole and pyridinium chemotypes allow for specific recognition of RNA motifs. As targeting RNA with small molecules is an extremely challenging area, these studies provide new information on RNA-ligand interactions that has many potential uses.

Design of a bioactive small molecule that targets r(AUUCU) repeats in spinocerebellar ataxia 10.

PubMed

Yang, Wang-Yong; Gao, Rui; Southern, Mark; Sarkar, Partha S; Disney, Matthew D

2016-06-01

RNA is an important target for chemical probes of function and lead therapeutics; however, it is difficult to target with small molecules. One approach to tackle this problem is to identify compounds that target RNA structures and utilize them to multivalently target RNA. Here we show that small molecules can be identified to selectively bind RNA base pairs by probing a library of RNA-focused small molecules. A small molecule that selectively binds AU base pairs informed design of a dimeric compound (2AU-2) that targets the pathogenic RNA, expanded r(AUUCU) repeats, that causes spinocerebellar ataxia type 10 (SCA10) in patient-derived cells. Indeed, 2AU-2 (50 nM) ameliorates various aspects of SCA10 pathology including improvement of mitochondrial dysfunction, reduced activation of caspase 3, and reduction of nuclear foci. These studies provide a first-in-class chemical probe to study SCA10 RNA toxicity and potentially define broadly applicable compounds targeting RNA AU base pairs in cells.

Identifying the Preferred RNA Motifs and Chemotypes that Interact by Probing Millions of Combinations

PubMed Central

Tran, Tuan; Disney, Matthew D.

2012-01-01

RNA is an important therapeutic target but information about RNA-ligand interactions is limited. Here we report a screening method that probes over 3,000,000 combinations of RNA motif-small molecule interactions to identify the privileged RNA structures and chemical spaces that interact. Specifically, a small molecule library biased for binding RNA was probed for binding to over 70,000 unique RNA motifs in a high throughput solution-based screen. The RNA motifs that specifically bind each small molecule were identified by microarray-based selection. In this library-versus-library or multidimensional combinatorial screening approach, hairpin loops (amongst a variety of RNA motifs) were the preferred RNA motif space that binds small molecules. Furthermore, it was shown that indole, 2-phenyl indole, 2-phenyl benzimidazole, and pyridinium chemotypes allow for specific recognition of RNA motifs. Since targeting RNA with small molecules is an extremely challenging area, these studies provide new information on RNA-ligand interactions that has many potential uses. PMID:23047683

Small-Molecule-Directed Hepatocyte-Like Cell Differentiation of Human Pluripotent Stem Cells.

PubMed

Mathapati, Santosh; Siller, Richard; Impellizzeri, Agata A R; Lycke, Max; Vegheim, Karianne; Almaas, Runar; Sullivan, Gareth J

2016-08-17

Hepatocyte-like cells (HLCs) generated in vitro from human pluripotent stem cells (hPSCs) provide an invaluable resource for basic research, regenerative medicine, drug screening, toxicology, and modeling of liver disease and development. This unit describes a small-molecule-driven protocol for in vitro differentiation of hPSCs into HLCs without the use of growth factors. hPSCs are coaxed through a developmentally relevant route via the primitive streak to definitive endoderm (DE) using the small molecule CHIR99021 (a Wnt agonist), replacing the conventional growth factors Wnt3A and activin A. The small-molecule-derived DE is then differentiated to hepatoblast-like cells in the presence of dimethyl sulfoxide. The resulting hepatoblasts are then differentiated to HLCs with N-hexanoic-Tyr, Ile-6 aminohexanoic amide (Dihexa, a hepatocyte growth factor agonist) and dexamethasone. The protocol provides an efficient and reproducible procedure for differentiation of hPSCs into HLCs utilizing small molecules. © 2016 by John Wiley & Sons, Inc. Copyright © 2016 John Wiley & Sons, Inc.

Bioorthogonal cyclization-mediated in situ self-assembly of small-molecule probes for imaging caspase activity in vivo

NASA Astrophysics Data System (ADS)

Ye, Deju; Shuhendler, Adam J.; Cui, Lina; Tong, Ling; Tee, Sui Seng; Tikhomirov, Grigory; Felsher, Dean W.; Rao, Jianghong

2014-06-01

Directed self-assembly of small molecules in living systems could enable a myriad of applications in biology and medicine, and already this has been used widely to synthesize supramolecules and nano/microstructures in solution and in living cells. However, controlling the self-assembly of synthetic small molecules in living animals is challenging because of the complex and dynamic in vivo physiological environment. Here we employ an optimized first-order bioorthogonal cyclization reaction to control the self-assembly of a fluorescent small molecule, and demonstrate its in vivo applicability by imaging caspase-3/7 activity in human tumour xenograft mouse models of chemotherapy. The fluorescent nanoparticles assembled in situ were imaged successfully in both apoptotic cells and tumour tissues using three-dimensional structured illumination microscopy. This strategy combines the advantages offered by small molecules with those of nanomaterials and should find widespread use for non-invasive imaging of enzyme activity in vivo.

9,10-Azaboraphenanthrene-containing small molecules and conjugated polymers: synthesis and their application in chemodosimeters for the ratiometric detection of fluoride ions.

PubMed

Zhang, Weidong; Li, Guoping; Xu, Letian; Zhuo, Yue; Wan, Wenming; Yan, Ni; He, Gang

2018-05-21

The introduction of main group elements into conjugated scaffolds is emerging as a key route to novel optoelectronic materials. Herein, an efficient and versatile way to synthesize polymerizable 9,10-azaboraphenanthrene ( BNP )-containing monomers by aromaticity-driven ring expansion reactions between highly antiaromatic borafluorene and azides is reported, and the corresponding conjugated small molecules and polymers are developed as well. The BNP -containing small molecules and conjugated polymers showed good air/moisture stability and notable fluorescence properties. Addition of fluoride ions to the BNP -based small molecules and polymers induced a rapid change in the emission color from blue to green/yellow, respectively, accompanied by strong intensity changes. The conjugated polymers showed better ratiometric sensing performance than small molecules due to the exciton migration along the conjugated chains. Further experiments showed that the sensing process is fully reversible. The films prepared by solution-deposition of BNP -based compounds in the presence of polycaprolactone also showed good ratiometric sensing for fluoride ions.

Small molecules enhance CRISPR genome editing in pluripotent stem cells.

PubMed

Yu, Chen; Liu, Yanxia; Ma, Tianhua; Liu, Kai; Xu, Shaohua; Zhang, Yu; Liu, Honglei; La Russa, Marie; Xie, Min; Ding, Sheng; Qi, Lei S

2015-02-05

The bacterial CRISPR-Cas9 system has emerged as an effective tool for sequence-specific gene knockout through non-homologous end joining (NHEJ), but it remains inefficient for precise editing of genome sequences. Here we develop a reporter-based screening approach for high-throughput identification of chemical compounds that can modulate precise genome editing through homology-directed repair (HDR). Using our screening method, we have identified small molecules that can enhance CRISPR-mediated HDR efficiency, 3-fold for large fragment insertions and 9-fold for point mutations. Interestingly, we have also observed that a small molecule that inhibits HDR can enhance frame shift insertion and deletion (indel) mutations mediated by NHEJ. The identified small molecules function robustly in diverse cell types with minimal toxicity. The use of small molecules provides a simple and effective strategy to enhance precise genome engineering applications and facilitates the study of DNA repair mechanisms in mammalian cells. Copyright © 2015 Elsevier Inc. All rights reserved.

Genome-Scale Architecture of Small Molecule Regulatory Networks and the Fundamental Trade-Off between Regulation and Enzymatic Activity

DOE PAGES

Reznik, Ed; Christodoulou, Dimitris; Goldford, Joshua E.; ...

2017-09-12

Metabolic flux is in part regulated by endogenous small molecules that modulate the catalytic activity of an enzyme, e.g., allosteric inhibition. In contrast to transcriptional regulation of enzymes, technical limitations have hindered the production of a genome-scale atlas of small molecule-enzyme regulatory interactions. Here, we develop a framework leveraging the vast, but fragmented, biochemical literature to reconstruct and analyze the small molecule regulatory network (SMRN) of the model organism Escherichia coli, including the primary metabolite regulators and enzyme targets. Using metabolic control analysis, we prove a fundamental trade-off between regulation and enzymatic activity, and we combine it with metabolomic measurementsmore » and the SMRN to make inferences on the sensitivity of enzymes to their regulators. By generalizing the analysis to other organisms, we identify highly conserved regulatory interactions across evolutionarily divergent species, further emphasizing a critical role for small molecule interactions in the maintenance of metabolic homeostasis.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chang, Yung-Ting; Department of Electrical Engineering, Graduate Institute of Photonics and Optoelectronics, National Taiwan University, Taipei, Taiwan 10617, Taiwan; Liu, Shun-Wei

Single-layer blue phosphorescence organic light emitting diodes (OLEDs) with either small-molecule or polymer hosts are fabricated using solution process and the performances of devices with different hosts are investigated. The small-molecule device exhibits luminous efficiency of 14.7 cd/A and maximum power efficiency of 8.39 lm/W, which is the highest among blue phosphorescence OLEDs with single-layer solution process and small molecular hosts. Using the same solution process for all devices, comparison of light out-coupling enhancement, with brightness enhancement film (BEF), between small-molecule and polymer based OLEDs is realized. Due to different dipole orientation and anisotropic refractive index, polymer-based OLEDs would trap less lightmore » than small molecule-based OLEDs internally, about 37% better based simulation results. In spite of better electrical and spectroscopic characteristics, including ambipolar characteristics, higher carrier mobility, higher photoluminescence quantum yield, and larger triplet state energy, the overall light out-coupling efficiency of small molecule-based devices is worse than that of polymer-based devices without BEF. However, with BEF for light out-coupling enhancement, the improved ratio in luminous flux and luminous efficiency for small molecule based device is 1.64 and 1.57, respectively, which are significantly better than those of PVK (poly-9-vinylcarbazole) devices. In addition to the theoretical optical simulation, the experimental data also confirm the origins of differential light-outcoupling enhancement. The maximum luminous efficiency and power efficiency are enhanced from 14.7 cd/A and 8.39 lm/W to 23 cd/A and 13.2 lm/W, respectively, with laminated BEF, which are both the highest so far for single-layer solution-process blue phosphorescence OLEDs with small molecule hosts.« less

Plasmonic Aptamer-Gold Nanoparticle Sensors for Small Molecule Fingerprint Identification

DTIC Science & Technology

2014-08-01

AFRL-RH-WP-TR-2014-0107 PLASMONIC APTAMER -GOLD NANOPARTICLE SENSORS FOR SMALL MOLECULE FINGERPRINT IDENTIFICATION Jorge Chávez Grant Slusher...Plasmonic Aptamer -Gold Nanoparticle Sensors for Small Molecule Fingerprint Identification 5a. CONTRACT NUMBER N/A 5b. GRANT NUMBER 5c. PROGRAM...The utilization of the plasmonic response of aptamer -gold nanoparticle conjugates (Apt-AuNPs) to design cross- reactive arrays for fingerprint

Covalent small-molecule-RNA complex formation enables cellular profiling of small-molecule-RNA interactions.

PubMed

Guan, Lirui; Disney, Matthew D

2013-09-16

Won't let you go! A strategy is described to design small molecules that react with their cellular RNA targets. This approach not only improves the activity of compounds targeting RNA in cell culture by a factor of about 2500 but also enables cell-wide profiling of its RNA targets. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Re-education begins at home: an overview of the discovery of in vivo-active small molecule modulators of endogenous stem cells.

PubMed

Um, JungIn; Lee, Ji-Hyung; Jung, Da-Woon; Williams, Darren R

2018-04-01

Degenerative diseases, such as Alzheimer's disease, heart disease and arthritis cause great suffering and are major socioeconomic burdens. An attractive treatment approach is stem cell transplantation to regenerate damaged or destroyed tissues. However, this can be problematic. For example, donor cells may not functionally integrate into the host tissue. An alternative methodology is to deliver bioactive agents, such as small molecules, directly into the diseased tissue to enhance the regenerative potential of endogenous stem cells. Areas covered: In this review, the authors discuss the necessity of developing these small molecules to treat degenerative diseases and survey progress in their application as therapeutics. They describe both the successes and caveats of developing small molecules that target endogenous stem cells to induce tissue regeneration. This article is based on literature searches which encompass databases for biomedical research and clinical trials. These small molecules are also categorized per their target disease and mechanism of action. Expert opinion: The development of small molecules targeting endogenous stem cells is a high-profile research area. Some compounds have made the successful transition to the clinic. Novel approaches, such as modulating the stem cell niche or targeted delivery to disease sites, should increase the likelihood of future successes in this field.

Bottom-up design of small molecules that stimulate exon 10 skipping in mutant MAPT pre-mRNA.

PubMed

Luo, Yiling; Disney, Matthew D

2014-09-22

One challenge in chemical biology is to develop small molecules that control cellular protein content. The amount and identity of proteins are influenced by the RNAs that encode them; thus, protein content in a cell could be affected by targeting mRNA. However, RNA has been traditionally difficult to target with small molecules. In this report, we describe controlling the protein products of the mutated microtubule-associated protein tau (MAPT) mature mRNA with a small molecule. MAPT mutations in exon 10 are associated with inherited frontotemporal dementia and Parkinsonism linked to chromosome 17 (FTDP-17), an incurable disease that is directly caused by increased inclusion of exon 10 in MAPT mRNA. Recent studies have shown that mutations within a hairpin at the MAPT exon 10-intron junction decrease the thermodynamic stability of the RNA, increasing binding to U1 snRNP and thus exon 10 inclusion. Therefore, we designed small molecules that bind and stabilize a mutant MAPT by using Inforna, a computational approach based on information about RNA-small-molecule interactions. The optimal compound selectively bound the mutant MAPT hairpin and thermodynamically stabilized its folding, facilitating exon 10 exclusion. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Small Molecule Supplements Improve Cultured Megakaryocyte Polyploidization by Modulating Multiple Cell Cycle Regulators.

PubMed

Zou, Xiaojing; Qu, Mingyi; Fang, Fang; Fan, Zeng; Chen, Lin; Yue, Wen; Xie, Xiaoyan; Pei, Xuetao

2017-01-01

Platelets (PLTs) are produced by megakaryocytes (MKs) that completed differentiation and endomitosis. Endomitosis is an important process in which the cell replicates its DNA without cytokinesis and develops highly polyploid MK. In this study, to gain a better PLTs production, four small molecules (Rho-Rock inhibitor (RRI), nicotinamide (NIC), Src inhibitor (SI), and Aurora B inhibitor (ABI)) and their combinations were surveyed as MK culture supplements for promoting polyploidization. Three leukemia cell lines as well as primary mononuclear cells were chosen in the function and mechanism studies of the small molecules. In an optimal culture method, cells were treated with different small molecules and their combinations. The impact of the small molecules on megakaryocytic surface marker expression, polyploidy, proliferation, and apoptosis was examined for the best MK polyploidization supplement. The elaborate analysis confirmed that the combination of SI and RRI together with our MK induction system might result in efficient ploidy promotion. Our experiments demonstrated that, besides direct downregulation on the expression of cytoskeleton protein actin, SI and RRI could significantly enhance the level of cyclins through the suppression of p53 and p21. The verified small molecule combination might be further used in the in vitro PLT manufacture and clinical applications.

Small Molecule Supplements Improve Cultured Megakaryocyte Polyploidization by Modulating Multiple Cell Cycle Regulators

PubMed Central

Fang, Fang; Chen, Lin; Yue, Wen

2017-01-01

Platelets (PLTs) are produced by megakaryocytes (MKs) that completed differentiation and endomitosis. Endomitosis is an important process in which the cell replicates its DNA without cytokinesis and develops highly polyploid MK. In this study, to gain a better PLTs production, four small molecules (Rho-Rock inhibitor (RRI), nicotinamide (NIC), Src inhibitor (SI), and Aurora B inhibitor (ABI)) and their combinations were surveyed as MK culture supplements for promoting polyploidization. Three leukemia cell lines as well as primary mononuclear cells were chosen in the function and mechanism studies of the small molecules. In an optimal culture method, cells were treated with different small molecules and their combinations. The impact of the small molecules on megakaryocytic surface marker expression, polyploidy, proliferation, and apoptosis was examined for the best MK polyploidization supplement. The elaborate analysis confirmed that the combination of SI and RRI together with our MK induction system might result in efficient ploidy promotion. Our experiments demonstrated that, besides direct downregulation on the expression of cytoskeleton protein actin, SI and RRI could significantly enhance the level of cyclins through the suppression of p53 and p21. The verified small molecule combination might be further used in the in vitro PLT manufacture and clinical applications. PMID:29201898

Small Molecules Affect Human Dental Pulp Stem Cell Properties Via Multiple Signaling Pathways

PubMed Central

Al-Habib, Mey; Yu, Zongdong

2013-01-01

One fundamental issue regarding stem cells for regenerative medicine is the maintenance of stem cell stemness. The purpose of the study was to test whether small molecules can enhance stem cell properties of mesenchymal stem cells (MSCs) derived from human dental pulp (hDPSCs), which have potential for multiple clinical applications. We identified the effects of small molecules (Pluripotin (SC1), 6-bromoindirubin-3-oxime and rapamycin) on the maintenance of hDPSC properties in vitro and the mechanisms involved in exerting the effects. Primary cultures of hDPSCs were exposed to optimal concentrations of these small molecules. Treated hDPSCs were analyzed for their proliferation, the expression levels of pluripotent and MSC markers, differentiation capacities, and intracellular signaling activations. We found that small molecule treatments decreased cell proliferation and increased the expression of STRO-1, NANOG, OCT4, and SOX2, while diminishing cell differentiation into odonto/osteogenic, adipogenic, and neurogenic lineages in vitro. These effects involved Ras-GAP-, ERK1/2-, and mTOR-signaling pathways, which may preserve the cell self-renewal capacity, while suppressing differentiation. We conclude that small molecules appear to enhance the immature state of hDPSCs in culture, which may be used as a strategy for adult stem cell maintenance and extend their capacity for regenerative applications. PMID:23573877

Methodologies for Studying B. subtilis Biofilms as a Model for Characterizing Small Molecule Biofilm Inhibitors.

PubMed

Bucher, Tabitha; Kartvelishvily, Elena; Kolodkin-Gal, Ilana

2016-10-09

This work assesses different methodologies to study the impact of small molecule biofilm inhibitors, such as D-amino acids, on the development and resilience of Bacillus subtilis biofilms. First, methods are presented that select for small molecule inhibitors with biofilm-specific targets in order to separate the effect of the small molecule inhibitors on planktonic growth from their effect on biofilm formation. Next, we focus on how inoculation conditions affect the sensitivity of multicellular, floating B. subtilis cultures to small molecule inhibitors. The results suggest that discrepancies in the reported effects of such inhibitors such as D-amino acids are due to inconsistent pre-culture conditions. Furthermore, a recently developed protocol is described for evaluating the contribution of small molecule treatments towards biofilm resistance to antibacterial substances. Lastly, scanning electron microscopy (SEM) techniques are presented to analyze the three-dimensional spatial arrangement of cells and their surrounding extracellular matrix in a B. subtilis biofilm. SEM facilitates insight into the three-dimensional biofilm architecture and the matrix texture. A combination of the methods described here can greatly assist the study of biofilm development in the presence and absence of biofilm inhibitors, and shed light on the mechanism of action of these inhibitors.

Electronic Structure of Small Lanthanide Containing Molecules

NASA Astrophysics Data System (ADS)

Kafader, Jared O.; Ray, Manisha; Topolski, Josey E.; Chick Jarrold, Caroline

2016-06-01

Lanthanide-based materials have unusual electronic properties because of the high number of electronic degrees of freedom arising from partial occupation of 4f orbitals, which make these materials optimal for their utilization in many applications including electronics and catalysis. Electronic spectroscopy of small lanthanide molecules helps us understand the role of these 4f electrons, which are generally considered core-like because of orbital contraction, but are energetically similar to valence electrons. The spectroscopy of small lanthanide-containing molecules is relatively unexplored and to broaden this understanding we have completed the characterization of small cerium, praseodymium, and europium molecules using photoelectron spectroscopy coupled with DFT calculations. The characterization of PrO, EuH, EuO/EuOH, and CexOy molecules have allowed for the determination of their electron affinity, the assignment of numerous anion to neutral state transitions, modeling of anion/neutral structures and electron orbital occupation.

System dynamics of subcellular transport.

PubMed

Chen, Vivien Y; Khersonsky, Sonya M; Shedden, Kerby; Chang, Young Tae; Rosania, Gus R

2004-01-01

In pharmacokinetic experiments, interpretations often hinge on treating cells as a "black box": a single, lumped compartment or boundary. Here, a combinatorial library of fluorescent small molecules was used to visualize subcellular transport pathways in living cells, using a kinetic, high content imaging system to monitor spatiotemporal variations of intracellular probe distribution. Most probes accumulate in cytoplasmic vesicles and probe kinetics conform to a nested, two-compartment dynamical system. At steady state, probes preferentially partition from the extracellular medium to the cytosol, and from the cytosol to cytoplasmic vesicles, with hydrophobic molecules favoring sequestration. Altogether, these results point to a general organizing principle underlying the system dynamics of subcellular, small molecule transport. In addition to plasma membrane permeability, subcellular transport phenomena can determine the active concentration of small molecules in the cytosol and the efflux of small molecules from cells. Fundamentally, direct observation of intracellular probe distribution challenges the simple boundary model of classical pharmacokinetics, which considers cells as static permeability barriers.

Effects of monohydric alcohols and polyols on the thermal stability of a protein

DOE Office of Scientific and Technical Information (OSTI.GOV)

Murakami, Shota; Kinoshita, Masahiro, E-mail: kinoshit@iae.kyoto-u.ac.jp

2016-03-28

The thermal stability of a protein is lowered by the addition of a monohydric alcohol, and this effect becomes larger as the size of hydrophobic group in an alcohol molecule increases. By contrast, it is enhanced by the addition of a polyol possessing two or more hydroxyl groups per molecule, and this effect becomes larger as the number of hydroxyl groups increases. Here, we show that all of these experimental observations can be reproduced even in a quantitative sense by rigid-body models focused on the entropic effect originating from the translational displacement of solvent molecules. The solvent is either puremore » water or water-cosolvent solution. Three monohydric alcohols and five polyols are considered as cosolvents. In the rigid-body models, a protein is a fused hard spheres accounting for the polyatomic structure in the atomic detail, and the solvent is formed by hard spheres or a binary mixture of hard spheres with different diameters. The effective diameter of cosolvent molecules and the packing fractions of water and cosolvent, which are crucially important parameters, are carefully estimated using the experimental data of properties such as the density of solid crystal of cosolvent, parameters in the pertinent cosolvent-cosolvent interaction potential, and density of water-cosolvent solution. We employ the morphometric approach combined with the integral equation theory, which is best suited to the physical interpretation of the calculation result. It is argued that the degree of solvent crowding in the bulk is the key factor. When it is made more serious by the cosolvent addition, the solvent-entropy gain upon protein folding is magnified, leading to the enhanced thermal stability. When it is made less serious, the opposite is true. The mechanism of the effects of monohydric alcohols and polyols is physically the same as that of sugars. However, when the rigid-body models are employed for the effect of urea, its addition is predicted to enhance the thermal stability, which conflicts with the experimental fact. We then propose, as two essential factors, not only the solvent-entropy gain but also the loss of protein-solvent interaction energy upon protein folding. The competition of changes in these two factors induced by the cosolvent addition determines the thermal-stability change.« less

Effects of monohydric alcohols and polyols on the thermal stability of a protein

NASA Astrophysics Data System (ADS)

Murakami, Shota; Kinoshita, Masahiro

2016-03-01

The thermal stability of a protein is lowered by the addition of a monohydric alcohol, and this effect becomes larger as the size of hydrophobic group in an alcohol molecule increases. By contrast, it is enhanced by the addition of a polyol possessing two or more hydroxyl groups per molecule, and this effect becomes larger as the number of hydroxyl groups increases. Here, we show that all of these experimental observations can be reproduced even in a quantitative sense by rigid-body models focused on the entropic effect originating from the translational displacement of solvent molecules. The solvent is either pure water or water-cosolvent solution. Three monohydric alcohols and five polyols are considered as cosolvents. In the rigid-body models, a protein is a fused hard spheres accounting for the polyatomic structure in the atomic detail, and the solvent is formed by hard spheres or a binary mixture of hard spheres with different diameters. The effective diameter of cosolvent molecules and the packing fractions of water and cosolvent, which are crucially important parameters, are carefully estimated using the experimental data of properties such as the density of solid crystal of cosolvent, parameters in the pertinent cosolvent-cosolvent interaction potential, and density of water-cosolvent solution. We employ the morphometric approach combined with the integral equation theory, which is best suited to the physical interpretation of the calculation result. It is argued that the degree of solvent crowding in the bulk is the key factor. When it is made more serious by the cosolvent addition, the solvent-entropy gain upon protein folding is magnified, leading to the enhanced thermal stability. When it is made less serious, the opposite is true. The mechanism of the effects of monohydric alcohols and polyols is physically the same as that of sugars. However, when the rigid-body models are employed for the effect of urea, its addition is predicted to enhance the thermal stability, which conflicts with the experimental fact. We then propose, as two essential factors, not only the solvent-entropy gain but also the loss of protein-solvent interaction energy upon protein folding. The competition of changes in these two factors induced by the cosolvent addition determines the thermal-stability change.

Activation of Polymine Catabolism as a Novel Strategy for Treating and/or Preventing Human Prostate Cancer

DTIC Science & Technology

2006-03-01

strategy against prostate cancer and thus, worthy of small molecule discovery and development. On the basis of findings obtained over the past 3...support for the discovery and development of specific small molecule inducers of SSAT as a novel therapeutic strategy targeting prostate cancer. This...D. Unscheduled Findings. Findings under Tasks 1 and 3 provided genetic evidence for the discovery and development of small molecule inducers of

A-D-A small molecules for solution-processed organic photovoltaic cells.

PubMed

Ni, Wang; Wan, Xiangjian; Li, Miaomiao; Wang, Yunchuang; Chen, Yongsheng

2015-03-25

A-D-A small molecules have drawn more and more attention in solution-processed organic solar cells due to the advantages of a diversity of structures, easy control of energy levels, etc. Recently, a power conversion efficiency of nearly 10% has been achieved through careful material design and device optimization. This feature article reviews recent representative progress in the design and application of A-D-A small molecules in organic photovoltaic cells.

Delivery of small molecules for bone regenerative engineering: preclinical studies and potential clinical applications

PubMed Central

Laurencin, Cato T.; Ashe, Keshia M.; Henry, Nicole; Kan, Ho Man; Lo, Kevin W-H.

2014-01-01

Stimulation of bone regeneration using growth factors is a promising approach for musculoskeletal regenerative engineering. Common limitations with protein growth factors are high manufacturing costs, protein instability, contamination issues, and unwanted immunogenic responses of the host. New strategies for bone regeneration that obviate these problems can have a significant impact on the treatment of skeletal injury and diseases. Over the past decade, a large number of small molecules with the potential of regenerating skeletal tissue have been reported in the literature. Here, we review this literature, paying specific attention to the prospects for small molecule-based bone-regenerative engineering. We also review the preclinical study of small molecules associated with bone regeneration. PMID:24508820

Cobalt coated substrate for matrix-free analysis of small molecules by laser desorption/ionization mass spectrometry

NASA Astrophysics Data System (ADS)

Yalcin, Talat; Li, Liang

2009-12-01

Small molecule analysis is one of the most challenging issues in matrix-assisted laser desorption/ionization (MALDI) mass spectrometry. We have developed a cobalt coated substrate as a target for matrix-free analysis of small molecules in laser desorption/ionization mass spectrometry. Cobalt coating of 60-70 nm thickness has been characterized by scanning electron microscopy, energy dispersive X-ray analysis, X-ray diffraction, and laser induced breakdown spectroscopy. This target facilitates hundreds of samples to be spotted and analyzed without mixing any matrices, in a very short time. This can save a lot of time and money and can be a very practical approach for the analysis of small molecules by laser desorption/ionization mass spectrometry.

Combinatorics of feedback in cellular uptake and metabolism of small molecules.

PubMed

Krishna, Sandeep; Semsey, Szabolcs; Sneppen, Kim

2007-12-26

We analyze the connection between structure and function for regulatory motifs associated with cellular uptake and usage of small molecules. Based on the boolean logic of the feedback we suggest four classes: the socialist, consumer, fashion, and collector motifs. We find that the socialist motif is good for homeostasis of a useful but potentially poisonous molecule, whereas the consumer motif is optimal for nutrition molecules. Accordingly, examples of these motifs are found in, respectively, the iron homeostasis system in various organisms and in the uptake of sugar molecules in bacteria. The remaining two motifs have no obvious analogs in small molecule regulation, but we illustrate their behavior using analogies to fashion and obesity. These extreme motifs could inspire construction of synthetic systems that exhibit bistable, history-dependent states, and homeostasis of flux (rather than concentration).

Trace element analysis of human urine collected after administration of Gd-based MRI contrast agents: characterizing spectral interferences using inorganic mass spectrometry

PubMed Central

Steuerwald, Amy J.; Parsons, Patrick J.; Arnason, John G.; Chen, Zhen; Peterson, C. Matthew; Louis, Germaine M. Buck

2013-01-01

Analysis of human urine is commonly used in biomonitoring studies to assess exposure to essential (e.g., Cu, Zn, Se) and non-essential (Pb, Cd, Pt) trace elements. These data are also used in epidemiological studies to evaluate potential associations between trace element exposure and various health outcomes within a population. Today most trace element analyses are typically performed using quadrupole-based inductively coupled plasma mass spectrometry (Q-ICP-MS). However, there is always the potential for spectral interferences with Q-ICP-MS instrumentation, especially when analyzing human specimens that may contain medications and other exogenous substances. Moreover, such xenobiotics may be unknown to the investigators. In a recent study focusing on environmental exposures and endometriosis: Endometriosis: Natural History, Diagnosis, and Outcomes (ENDO Study), urine specimens (n=619) were collected from participating women upon enrollment into the study or prior to surgery or pelvic magnetic resonance imaging (MRI), and analyzed for 21 trace elements by Q-ICP-MS. Here we report on some anomalous results observed for Se and Pt with elevated concentrations up to several orders of magnitude greater than what might be expected based on established reference intervals. Further investigations using Sector Field (SF-) ICP-MS instrumentation led to identification of doubly charged and polyatomic gadolinium (Gd) species traced to a Gd-based contrast agent that was administered to some subjects just prior to urine collection. Specifically, interferences from Gd2+ and several minor polyatomics were identified as interferences on all of the major isotopes of Se including 74Se, 76Se, 77Se, 78Se, 80Se, and 82Se. While trace amounts of Pt were present in the urine, a number of Gd-containing polyatomic species were also evident as major interferences on all isotopes of Pt (190Pt, 192Pt, 194Pt, 195Pt, 196Pt, and 198Pt), including Gd-chlorides, Gd-argides, and Gd-oxides. These observations underscore the importance of considering potential isobaric interferences when interpreting unusual trace element results for clinical specimens. PMID:27397951

Quantum control of molecular fragmentation in strong laser fields

NASA Astrophysics Data System (ADS)

Zohrabi, Mohammad

Present advances in laser technology allow the production of ultrashort (<˜5 fs, approaching single cycle at 800 nm), intense tabletop laser pulses. At these high intensities laser-matter interactions cannot be described with perturbation theory since multiphoton processes are involved. This is in contrast to photodissociation by the absorption of a single photon, which is well described by perturbation theory. For example, at high intensities (<˜5x1013 W/cm2) the fragmentation of molecular hydrogen ions has been observed via the absorption of three or more photons. In another example, an intriguing dissociation mechanism has been observed where molecular hydrogen ions seem to fragment by apparently absorbing no photons. This is actually a two photon process, photoabsorption followed by stimulated emission, resulting in low energy fragments. We are interested in exploring these kinds of multiphoton processes. Our research group has studied the dynamics and control of fragmentation induced by strong laser fields in a variety of molecular targets. The main goal is to provide a basic understanding of fragmentation mechanisms and possible control schemes of benchmark systems such as H2+. This knowledge is further extended to more complex systems like the benchmark H3+ polyatomic and other molecules. In this dissertation, we report research based on two types of experiments. In the first part, we describe laser-induced fragmentation of molecular ion-beam targets. In the latter part, we discuss the formation of highly-excited neutral fragments from hydrogen molecules using ultrashort laser pulses. In carrying out these experiments, we have also extended experimental techniques beyond their previous capabilities. We have performed a few experiments to advance our understanding of laser-induced fragmentation of molecular-ion beams. For instance, we explored vibrationally resolved spectra of O2+ dissociation using various wavelengths. We observed a vibrational suppression effect in the dissociation spectra due to the small magnitude of the dipole transition moment, which depends on the photon energy --- a phenomenon known as Cooper minima. By changing the laser wavelength, the Cooper minima shift, a fact that was used to identify the dissociation pathways. In another project, we studied the carrier-envelope phase (CEP) dependences of highly-excited fragments from hydrogen molecules. General CEP theory predicts a CEP dependence in the total dissociation yield due to the interference of dissociation pathways differing by an even net number of photons, and our measurements are consistent with this prediction. Moreover, we were able to extract the difference in the net number of photons involved in the interfering pathways by using a Fourier analysis. In terms of our experimental method, we have implemented a pump-probe style technique on a thin molecular ion-beam target and explored the feasibility of such experiments. The results presented in this work should lead to a better understanding of the dynamics and control in molecular fragmentation induced by intense laser fields.

Chemical correction of pre-mRNA splicing defects associated with sequestration of muscleblind-like 1 protein by expanded r(CAG)-containing transcripts.

PubMed

Kumar, Amit; Parkesh, Raman; Sznajder, Lukasz J; Childs-Disney, Jessica L; Sobczak, Krzysztof; Disney, Matthew D

2012-03-16

Recently, it was reported that expanded r(CAG) triplet repeats (r(CAG)(exp)) associated with untreatable neurological diseases cause pre-mRNA mis-splicing likely due to sequestration of muscleblind-like 1 (MBNL1) splicing factor. Bioactive small molecules that bind the 5'CAG/3'GAC motif found in r(CAG)(exp) hairpin structure were identified by using RNA binding studies and virtual screening/chemical similarity searching. Specifically, a benzylguanidine-containing small molecule was found to improve pre-mRNA alternative splicing of MBNL1-sensitive exons in cells expressing the toxic r(CAG)(exp). The compound was identified by first studying the binding of RNA 1 × 1 nucleotide internal loops to small molecules known to have affinity for nucleic acids. Those studies identified 4',6-diamidino-2-phenylindole (DAPI) as a specific binder to RNAs with the 5'CAG/3'GAC motif. DAPI was then used as a query molecule in a shape- and chemistry alignment-based virtual screen to identify compounds with improved properties, which identified 4-guanidinophenyl 4-guanidinobenzoate, a small molecule that improves pre-mRNA splicing defects associated with the r(CAG)(exp)-MBNL1 complex. This compound may facilitate the development of therapeutics to treat diseases caused by r(CAG)(exp) and could serve as a useful chemical tool to dissect the mechanisms of r(CAG)(exp) toxicity. The approach used in these studies, defining the small RNA motifs that bind small molecules with known affinity for nucleic acids and then using virtual screening to optimize them for bioactivity, may be generally applicable for designing small molecules that target other RNAs in the human genomic sequence.

A Computational Investigation of Small-Molecule Engagement of Hot Spots at Protein-Protein Interaction Interfaces.

PubMed

Xu, David; Si, Yubing; Meroueh, Samy O

2017-09-25

The binding affinity of a protein-protein interaction is concentrated at amino acids known as hot spots. It has been suggested that small molecules disrupt protein-protein interactions by either (i) engaging receptor protein hot spots or (ii) mimicking hot spots of the protein ligand. Yet, no systematic studies have been done to explore how effectively existing small-molecule protein-protein interaction inhibitors mimic or engage hot spots at protein interfaces. Here, we employ explicit-solvent molecular dynamics simulations and end-point MM-GBSA free energy calculations to explore this question. We select 36 compounds for which high-quality binding affinity and cocrystal structures are available. Five complexes that belong to three classes of protein-protein interactions (primary, secondary, and tertiary) were considered, namely, BRD4•H4, XIAP•Smac, MDM2•p53, Bcl-xL•Bak, and IL-2•IL-2Rα. Computational alanine scanning using MM-GBSA identified hot-spot residues at the interface of these protein interactions. Decomposition energies compared the interaction of small molecules with individual receptor hot spots to those of the native protein ligand. Pharmacophore analysis was used to investigate how effectively small molecules mimic the position of hot spots of the protein ligand. Finally, we study whether small molecules mimic the effects of the native protein ligand on the receptor dynamics. Our results show that, in general, existing small-molecule inhibitors of protein-protein interactions do not optimally mimic protein-ligand hot spots, nor do they effectively engage protein receptor hot spots. The more effective use of hot spots in future drug design efforts may result in smaller compounds with higher ligand efficiencies that may lead to greater success in clinical trials.

Fine-tuning molecular acoustic models: sensitivity of the predicted attenuation to the Lennard-Jones parameters

NASA Astrophysics Data System (ADS)

Petculescu, Andi G.; Lueptow, Richard M.

2005-01-01

In a previous paper [Y. Dain and R. M. Lueptow, J. Acoust. Soc. Am. 109, 1955 (2001)], a model of acoustic attenuation due to vibration-translation and vibration-vibration relaxation in multiple polyatomic gas mixtures was developed. In this paper, the model is improved by treating binary molecular collisions via fully pairwise vibrational transition probabilities. The sensitivity of the model to small variations in the Lennard-Jones parameters-collision diameter (σ) and potential depth (ɛ)-is investigated for nitrogen-water-methane mixtures. For a N2(98.97%)-H2O(338 ppm)-CH4(1%) test mixture, the transition probabilities and acoustic absorption curves are much more sensitive to σ than they are to ɛ. Additionally, when the 1% methane is replaced by nitrogen, the resulting mixture [N2(99.97%)-H2O(338 ppm)] becomes considerably more sensitive to changes of σwater. The current model minimizes the underprediction of the acoustic absorption peak magnitudes reported by S. G. Ejakov et al. [J. Acoust. Soc. Am. 113, 1871 (2003)]. .

Cancer Theranostic Nanoparticles Self-Assembled from Amphiphilic Small Molecules with Equilibrium Shift-Induced Renal Clearance

PubMed Central

Ma, Yuan; Mou, Quanbing; Sun, Mo; Yu, Chunyang; Li, Jianqi; Huang, Xiaohua; Zhu, Xinyuan; Yan, Deyue; Shen, Jian

2016-01-01

Nano drug delivery systems have emerged as promising candidates for cancer therapy, whereas their uncertainly complete elimination from the body within specific timescales restricts their clinical translation. Compared with hepatic clearance of nanoparticles, renal excretion of small molecules is preferred to minimize the agent-induced toxicity. Herein, we construct in vivo renal-clearable nanoparticles, which are self-assembled from amphiphilic small molecules holding the capabilities of magnetic resonance imaging (MRI) and chemotherapy. The assembled nanoparticles can accumulate in tumor tissues for their nano-characteristics, while the small molecules dismantled from the nanoparticles can be efficiently cleared by kidneys. The renal-clearable nanoparticles exhibit excellent tumor-inhibition performance as well as low side effects and negligible chronic toxicity. These results demonstrate a potential strategy for small molecular nano drug delivery systems with obvious anticancer effect and low-toxic metabolism pathway for clinical applications. PMID:27446502

Molecular t-matrices for Low-Energy Electron Diffraction (TMOL v1.1)

NASA Astrophysics Data System (ADS)

Blanco-Rey, Maria; de Andres, Pedro; Held, Georg; King, David A.

2004-08-01

We describe a FORTRAN-90 program that computes scattering t-matrices for a molecule. These can be used in a Low-Energy Electron Diffraction program to solve the molecular structural problem very efficiently. The intramolecular multiple scattering is computed within a Dyson-like approach, using free space Green propagators in a basis of spherical waves. The advantage of this approach is related to exploiting the chemical identity of the molecule, and to the simplicity to translate and rotate these t-matrices without performing a new multiple-scattering calculation for each configuration. FORTRAN-90 routines for rotating the resulting t-matrices using Wigner matrices are also provided. Program summaryTitle of program: TMOL Catalogue number: ADUF Program summary URL:http://cpc.cs.qub.ac.uk/summaries/ADUF Program obtainable from: CPC Program Library, Queen's University of Belfast, N. Ireland. Computers: Alpha ev6-21264 (700 MHz) and Pentium-IV. Operating systems: Digital UNIX V5.0 and Linux (Red Hat 8.0). Programming language: FORTRAN-90/95 (Compaq True64 compiler, and Intel Fortran Compiler 7.0 for Linux). High-speed storage required for the test run: minimum 64 Mbytes, it can grow to more depending on the system considered. Disk storage required: None. No. of bits in a word: 64 and 32. No. of lines in distributed program, including test data etc.: 5404 No. of bytes in distributed program, including test data etc.: 59 856 Distribution format: tar.gz Nature of problem: We describe the FORTRAN-90 program TMOL (v1.1) for the computation of non-diagonal scattering t-matrices for molecules or any other poly-atomic sub-unit of surface structures. These matrices can be used in an standard Low-Energy Electron Diffraction program, such as LEED90 or CLEED. Method of solution: A general non-diagonal t-matrix is assumed for the atoms or more general scatterers forming the molecule. The molecular t-matrix is solved adding the possible intramolecular multiple scattering events using Green's propagator formalism. The resulting t-matrix is referred to the mass centre of the molecule and can be easily translated with these propagators and rotated applying Wigner matrices. Typical running time: Calculating the t-matrix for a single energy takes a few seconds. Time depends on the maximum angular momentum quantum number, lmax, and the number of scatterers in the molecule, N. Running time scales as lmax6 and N3. References: [1] S. Andersson, J.B. Pendry, J. Phys. C: Solid St. Phys. 13 (1980) 3547. [2] A. Gonis, W.H. Butler, Multiple Scattering in Solids, Springer-Verlag, Berlin/New York, 2000.

Effects of endogenous small molecular compounds on the rheological properties, texture and microstructure of soymilk coagulum: Removal of phytate using ultrafiltration.

PubMed

Wang, Ruican; Guo, Shuntang

2016-11-15

This study aims to clarify the roles played by endogenous small molecular components in soymilk coagulation process and the properties of gels. Soymilk samples with decreasing levels of small molecules were prepared by ultrafiltration, to reduce the amount of phytate and salts. CaSO4-induced coagulation process was analyzed using rheological methods. Results showed that removal of free small molecules decreased the activation energy of protein coagulation, resulting in accelerated reaction and increased gel strength. However, too fast a reaction led to the drop in storage modulus (G'). Microscopic observation suggested that accelerated coagulation generated a coarse and non-uniform gel network with large pores. This network could not hold much water, leading to serious syneresis. Endogenous small molecules in soymilk were vital in the fine gel structure. Coagulation rate could be controlled by adjusting the amount of small molecules to obtain tofu products with the optimal texture. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Optical Spectrum of SrOH Re-Visited Zeeman Effect, High-Resolution Spectroscopy and Franck-Condon Factors.

NASA Astrophysics Data System (ADS)

Nguyen, Trung; Kokkin, Damian L.; Steimle, Timothy; Kozyryev, Ivan; Doyle, John M.

2015-06-01

Motivated by a diverse range of applications in physics and chemistry, currently there is great interest in the cooling of molecules to very low temperatures (≤1 mK). Direct laser cooling has been previously demonstrated for the diatomic radicals SrF, YO, and CaF, and most recently a three-dimensional magneto-optical trap (MOT) of SrF molecules was achieved. To determine the possibility of laser cooling for polyatomic molecules containing three or more atoms, detailed information is required about their Franck-Condon factors (FCFs) for emission from the excited states of interest. Here we report on the high-resolution laser excitation spectra, recorded field-free and in the presence of a static magnetic field, and on the dispersed fluorescence (DF) spectra for the A^2Π1/2 ← X^2σ^+ and B^2σ^+ ← X ^2σ^+ electronic transitions of SrOH. The DF spectra were analyzed to precisely determine FCFs and compared with values predicted using a normal coordinate GF matrix approach. The recorded Zeeman spectra were analyzed to determine the magnetic moments. Implication for proposed laser cooling and trapping experiments for SrOH will be presented. E.S. Shuman, J.F. Barry and D. DeMille, Nature 467, 820 (2010) J.F. Barry, E.S. Shuman, E.B. Norrgard and D. DeMille, Phys. Rev. Lett. 108, 103002 (2012) M.T. Hummon, M. Yeo, B.K. Stuhl, A.L. Collopy, Y. Xia, and J. Ye, Phys. Rev. Lett. 110, 143001 (2013) M. Yeo, M.T. Hummon, A.L. Collopy, B. Yan, B. Hemmerling, E. Chae, J.M. Doyle, and J. Ye, arXiv:1501.04683 (2015) V. Zhelyazkova, A. Cournol, T.E. Wall, A. Matsushima, J.J. Hudson, E.A. Hinds, M.R. Tarbutt, and B.E. Sauer, Phys. Rev. A 89, 053416 (2014) J.F. Barry, D.J. McCarron, E.B. Norrgard, M.H. Steinecker and D. DeMille, Nature 512, 286 (2014) D.J. McCarron, E.B. Norrgard, M.H. Steinecker and D. DeMille, arXiv:1412.8220 (2014)

Gyration-radius dynamics in structural transitions of atomic clusters.

PubMed

Yanao, Tomohiro; Koon, Wang S; Marsden, Jerrold E; Kevrekidis, Ioannis G

2007-03-28

This paper is concerned with the structural transition dynamics of the six-atom Morse cluster with zero total angular momentum, which serves as an illustrative example of the general reaction dynamics of isolated polyatomic molecules. It develops a methodology that highlights the interplay between the effects of the potential energy topography and those of the intrinsic geometry of the molecular internal space. The method focuses on the dynamics of three coarse variables, the molecular gyration radii. By using the framework of geometric mechanics and hyperspherical coordinates, the internal motions of a molecule are described in terms of these three gyration radii and hyperangular modes. The gyration radii serve as slow collective variables, while the remaining hyperangular modes serve as rapidly oscillating "bath" modes. Internal equations of motion reveal that the gyration radii are subject to two different kinds of forces: One is the ordinary force that originates from the potential energy function of the system, while the other is an internal centrifugal force. The latter originates from the dynamical coupling of the gyration radii with the hyperangular modes. The effects of these two forces often counteract each other: The potential force generally works to keep the internal mass distribution of the system compact and symmetric, while the internal centrifugal force works to inflate and elongate it. Averaged fields of these two forces are calculated numerically along a reaction path for the structural transition of the molecule in the three-dimensional space of gyration radii. By integrating the sum of these two force fields along the reaction path, an effective energy curve is deduced, which quantifies the gross work necessary for the system to change its mass distribution along the reaction path. This effective energy curve elucidates the energy-dependent switching of the structural preference between symmetric and asymmetric conformations. The present methodology should be of wide use for the systematic reduction of dimensionality as well as for the identification of kinematic barriers associated with the rearrangement of mass distribution in a variety of molecular reaction dynamics in vacuum.

Gyration-radius dynamics in structural transitions of atomic clusters

NASA Astrophysics Data System (ADS)

Yanao, Tomohiro; Koon, Wang S.; Marsden, Jerrold E.; Kevrekidis, Ioannis G.

2007-03-01

This paper is concerned with the structural transition dynamics of the six-atom Morse cluster with zero total angular momentum, which serves as an illustrative example of the general reaction dynamics of isolated polyatomic molecules. It develops a methodology that highlights the interplay between the effects of the potential energy topography and those of the intrinsic geometry of the molecular internal space. The method focuses on the dynamics of three coarse variables, the molecular gyration radii. By using the framework of geometric mechanics and hyperspherical coordinates, the internal motions of a molecule are described in terms of these three gyration radii and hyperangular modes. The gyration radii serve as slow collective variables, while the remaining hyperangular modes serve as rapidly oscillating "bath" modes. Internal equations of motion reveal that the gyration radii are subject to two different kinds of forces: One is the ordinary force that originates from the potential energy function of the system, while the other is an internal centrifugal force. The latter originates from the dynamical coupling of the gyration radii with the hyperangular modes. The effects of these two forces often counteract each other: The potential force generally works to keep the internal mass distribution of the system compact and symmetric, while the internal centrifugal force works to inflate and elongate it. Averaged fields of these two forces are calculated numerically along a reaction path for the structural transition of the molecule in the three-dimensional space of gyration radii. By integrating the sum of these two force fields along the reaction path, an effective energy curve is deduced, which quantifies the gross work necessary for the system to change its mass distribution along the reaction path. This effective energy curve elucidates the energy-dependent switching of the structural preference between symmetric and asymmetric conformations. The present methodology should be of wide use for the systematic reduction of dimensionality as well as for the identification of kinematic barriers associated with the rearrangement of mass distribution in a variety of molecular reaction dynamics in vacuum.

Induction and reversal of myotonic dystrophy type 1 pre-mRNA splicing defects by small molecules.

PubMed

Childs-Disney, Jessica L; Stepniak-Konieczna, Ewa; Tran, Tuan; Yildirim, Ilyas; Park, HaJeung; Chen, Catherine Z; Hoskins, Jason; Southall, Noel; Marugan, Juan J; Patnaik, Samarjit; Zheng, Wei; Austin, Chris P; Schatz, George C; Sobczak, Krzysztof; Thornton, Charles A; Disney, Matthew D

2013-01-01

The ability to control pre-mRNA splicing with small molecules could facilitate the development of therapeutics or cell-based circuits that control gene function. Myotonic dystrophy type 1 is caused by the dysregulation of alternative pre-mRNA splicing due to sequestration of muscleblind-like 1 protein (MBNL1) by expanded, non-coding r(CUG) repeats (r(CUG)(exp)). Here we report two small molecules that induce or ameliorate alternative splicing dysregulation. A thiophene-containing small molecule (1) inhibits the interaction of MBNL1 with its natural pre-mRNA substrates. Compound (2), a substituted naphthyridine, binds r(CUG)(exp) and displaces MBNL1. Structural models show that 1 binds MBNL1 in the Zn-finger domain and that 2 interacts with UU loops in r(CUG)(exp). This study provides a structural framework for small molecules that target MBNL1 by mimicking r(CUG)(exp) and shows that targeting MBNL1 causes dysregulation of alternative splicing, suggesting that MBNL1 is thus not a suitable therapeutic target for the treatment of myotonic dystrophy type 1.

Induction and Reversal of Myotonic Dystrophy Type 1 Pre-mRNA Splicing Defects by Small Molecules

PubMed Central

Childs-Disney, Jessica L.; Stepniak-Konieczna, Ewa; Tran, Tuan; Yildirim, Ilyas; Park, HaJeung; Chen, Catherine Z.; Hoskins, Jason; Southall, Noel; Marugan, Juan J.; Patnaik, Samarjit; Zheng, Wei; Austin, Chris P.; Schatz, George C.; Sobczak, Krzysztof; Thornton, Charles A.; Disney, Matthew D.

2013-01-01

The ability to control pre-mRNA splicing with small molecules could facilitate the development of therapeutics or cell-based circuits that control gene function. Myotonic dystrophy type 1 (DM1) is caused by the dysregulation of alternative pre-mRNA splicing due to sequestration of muscleblind-like 1 protein (MBNL1) by expanded, non-coding r(CUG) repeats (r(CUG)exp). Here we report two small molecules that induce or ameliorate alternative splicing dysregulation. The thiophene-containing small molecule (1) inhibits the interaction of MBNL1 with its natural pre-mRNA substrates. Compound (2), a substituted naphthyridine, binds r(CUG)exp and displaces MBNL1. Structural models show that 1 binds MBNL1 in the Zn-finger domain and that 2 interacts with UU loops in r(CUG)exp. This study provides a structural framework for small molecules that target MBNL1 by mimicking r(CUG)exp and shows that targeting MBNL1 causes dysregulation of alternative splicing, suggesting that MBNL1 is thus not a suitable therapeutic target for the treatment of DM1. PMID:23806903

Selecting, Acquiring, and Using Small Molecule Libraries for High-Throughput Screening

PubMed Central

Dandapani, Sivaraman; Rosse, Gerard; Southall, Noel; Salvino, Joseph M.; Thomas, Craig J.

2015-01-01

The selection, acquisition and use of high quality small molecule libraries for screening is an essential aspect of drug discovery and chemical biology programs. Screening libraries continue to evolve as researchers gain a greater appreciation of the suitability of small molecules for specific biological targets, processes and environments. The decisions surrounding the make-up of any given small molecule library is informed by a multitude of variables and opinions vary on best-practices. The fitness of any collection relies upon upfront filtering to avoiding problematic compounds, assess appropriate physicochemical properties, install the ideal level of structural uniqueness and determine the desired extent of molecular complexity. These criteria are under constant evaluation and revision as academic and industrial organizations seek out collections that yield ever improving results from their screening portfolios. Practical questions including cost, compound management, screening sophistication and assay objective also play a significant role in the choice of library composition. This overview attempts to offer advice to all organizations engaged in small molecule screening based upon current best practices and theoretical considerations in library selection and acquisition. PMID:26705509

Selecting, Acquiring, and Using Small Molecule Libraries for High-Throughput Screening.

PubMed

Dandapani, Sivaraman; Rosse, Gerard; Southall, Noel; Salvino, Joseph M; Thomas, Craig J

The selection, acquisition and use of high quality small molecule libraries for screening is an essential aspect of drug discovery and chemical biology programs. Screening libraries continue to evolve as researchers gain a greater appreciation of the suitability of small molecules for specific biological targets, processes and environments. The decisions surrounding the make-up of any given small molecule library is informed by a multitude of variables and opinions vary on best-practices. The fitness of any collection relies upon upfront filtering to avoiding problematic compounds, assess appropriate physicochemical properties, install the ideal level of structural uniqueness and determine the desired extent of molecular complexity. These criteria are under constant evaluation and revision as academic and industrial organizations seek out collections that yield ever improving results from their screening portfolios. Practical questions including cost, compound management, screening sophistication and assay objective also play a significant role in the choice of library composition. This overview attempts to offer advice to all organizations engaged in small molecule screening based upon current best practices and theoretical considerations in library selection and acquisition.

Simulation-based cheminformatic analysis of organelle-targeted molecules: lysosomotropic monobasic amines.

PubMed

Zhang, Xinyuan; Zheng, Nan; Rosania, Gus R

2008-09-01

Cell-based molecular transport simulations are being developed to facilitate exploratory cheminformatic analysis of virtual libraries of small drug-like molecules. For this purpose, mathematical models of single cells are built from equations capturing the transport of small molecules across membranes. In turn, physicochemical properties of small molecules can be used as input to simulate intracellular drug distribution, through time. Here, with mathematical equations and biological parameters adjusted so as to mimic a leukocyte in the blood, simulations were performed to analyze steady state, relative accumulation of small molecules in lysosomes, mitochondria, and cytosol of this target cell, in the presence of a homogenous extracellular drug concentration. Similarly, with equations and parameters set to mimic an intestinal epithelial cell, simulations were also performed to analyze steady state, relative distribution and transcellular permeability in this non-target cell, in the presence of an apical-to-basolateral concentration gradient. With a test set of ninety-nine monobasic amines gathered from the scientific literature, simulation results helped analyze relationships between the chemical diversity of these molecules and their intracellular distributions.

Thermal Degradation of Small Molecules: A Global Metabolomic Investigation.

PubMed

Fang, Mingliang; Ivanisevic, Julijana; Benton, H Paul; Johnson, Caroline H; Patti, Gary J; Hoang, Linh T; Uritboonthai, Winnie; Kurczy, Michael E; Siuzdak, Gary

2015-11-03

Thermal processes are widely used in small molecule chemical analysis and metabolomics for derivatization, vaporization, chromatography, and ionization, especially in gas chromatography mass spectrometry (GC/MS). In this study the effect of heating was examined on a set of 64 small molecule standards and, separately, on human plasma metabolite extracts. The samples, either derivatized or underivatized, were heated at three different temperatures (60, 100, and 250 °C) at different exposure times (30 s, 60 s, and 300 s). All the samples were analyzed by liquid chromatography coupled to electrospray ionization mass spectrometry (LC/MS) and the data processed by XCMS Online ( xcmsonline.scripps.edu ). The results showed that heating at an elevated temperature of 100 °C had an appreciable effect on both the underivatized and derivatized molecules, and heating at 250 °C created substantial changes in the profile. For example, over 40% of the molecular peaks were altered in the plasma metabolite analysis after heating (250 °C, 300s) with a significant formation of degradation and transformation products. The analysis of 64 small molecule standards validated the temperature-induced changes observed on the plasma metabolites, where most of the small molecules degraded at elevated temperatures even after minimal exposure times (30 s). For example, tri- and diorganophosphates (e.g., adenosine triphosphate and adenosine diphosphate) were readily degraded into a mono-organophosphate (e.g., adenosine monophosphate) during heating. Nucleosides and nucleotides (e.g., inosine and inosine monophosphate) were also found to be transformed into purine derivatives (e.g., hypoxanthine). A newly formed transformation product, oleoyl ethyl amide, was identified in both the underivatized and derivatized forms of the plasma extracts and small molecule standard mixture, and was likely generated from oleic acid. Overall these analyses show that small molecules and metabolites undergo significant time-sensitive alterations when exposed to elevated temperatures, especially those conditions that mimic sample preparation and analysis in GC/MS experiments.

Comprehensive mass spectrometric analysis of novel organic semiconductor molecules

NASA Astrophysics Data System (ADS)

Prada, Svitlana

This work presents a comprehensive mass spectrometry (MS) study of novel organic semiconductor molecules including ion mobility/reactivity measurements and trace elemental analysis. The organic molecules investigated here are important semiconductor materials for molecular electronic devices such as Organic Field-Effect Transistors (OFETs) and Light Emitted Diodes (LED). A high-performance orthogonal time-of flight mass spectrometer (TOF-MS) in combination with a matrix assisted laser desorption/ionization (MALDI) source operating at elevated pressure was used to perform MALDI/TOF analyses of pentacene and some of its derivatives with and without an added matrix. The observation of ion-molecule reactions between "cold" analyte ions and neutral analyte molecules in the gas phase has provided some insight into the mechanism of pentacene cluster formation and its functionalized derivatives. Furthermore, some of the matrices employed to assist the desorption/ionization process of these compounds were observed to influence the outcome via ion-molecule reactions of analyte ions and matrix molecules in the gas phase. The stability and reactivity of the compounds and their clusters in the MALDI plume during gas-phase expansion were evaluated; possible structures of the resulting clusters are discussed. The MALDI/TOF technique was also helpful in distinguishing between two isomeric forms of bis-[(triisopropylsilyl)-ethynyl]-pentacene. Furthermore, we reported ion mobility measurements of functionalized pentacene ions with a modified triple quadrupole mass spectrometer fitted with an ion molecule reactor (IMR). The IMR is equipped with a variable axial electrostatic drift field (ADF) and is able to trap ions for a prolong period of time. These capabilities were successfully employed in the measurement of ion mobilities in different modes of the IMR operation. Theoretical modeling of the drift dynamics and the special localization of the large ion packet was successfully implemented. The contribution of the quadrupole RF field to the drift dynamics also was taken into consideration. The IMR was successfully employed in the ion-molecule reactions study of four functionalized pentacene derivatives such as TIPS, o-TIPS, 6,13-bis-[(triisopropylsilyl)-ethynyl]-pentacene-2,3-dicarbonitrile (TIPS(CN)2), and 6,13-bis-[(triisopropylsilyl)-ethynyl]-pentacene-2,3,9,10-tetracarbonitrile (TIPS(CN)4). Details of the IMR operation in this mode are extensively discussed. The purity of the starting material is one of the most important parameters for the fabrication of a molecular electronic device. We report the method of determination of trace elemental impurities (Li, Na, Al, Mg, Be, Pb, Mn, Co, Ti, Sn, Cu, Cr, V, Zn, Fe, Ca, K and Ni) in organic semiconductor materials, such as Tetracene, Anthracene, Pentacene, TIPS and Rubrene, using an inductively coupled plasma quadrupole mass spectrometer (ICP-MS) fitted with a dynamic reaction cell (DRC). The determination of Fe, Ca, K and Ni in the organic semiconductor materials was carried out using NH3 as a reaction gas in the DRC mode to obviate the effect of polyatomic isobaric interferences. The other trace elements such as Li, Na, Al, Mg, Be, Pb, Mn, Co, Ti, Sn, Cu, Cr, V and Zn have been determined under standard operating conditions.

Identification of small molecules capable of regulating conformational changes of telomeric G-quadruplex

NASA Astrophysics Data System (ADS)

Chen, Shuo-Bin; Liu, Guo-Cai; Gu, Lian-Quan; Huang, Zhi-Shu; Tan, Jia-Heng

2018-02-01

Design of small molecules targeted at human telomeric G-quadruplex DNA is an extremely active research area. Interestingly, the telomeric G-quadruplex is a highly polymorphic structure. Changes in its conformation upon small molecule binding may be a powerful method to achieve a desired biological effect. However, the rational development of small molecules capable of regulating conformational change of telomeric G-quadruplex structures is still challenging. In this study, we developed a reliable ligand-based pharmacophore model based on isaindigotone derivatives with conformational change activity toward telomeric G-quadruplex DNA. Furthermore, virtual screening of database was conducted using this pharmacophore model and benzopyranopyrimidine derivatives in the database were identified as a strong inducer of the telomeric G-quadruplex DNA conformation, transforming it from hybrid-type structure to parallel structure.

Protein Scaffolding for Small Molecule Catalysts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baker, David

We aim to design hybrid catalysts for energy production and storage that combine the high specificity, affinity, and tunability of proteins with the potent chemical reactivities of small organometallic molecules. The widely used Rosetta and RosettaDesign methodologies will be extended to model novel protein / small molecule catalysts in which one or many small molecule active centers are supported and coordinated by protein scaffolding. The promise of such hybrid molecular systems will be demonstrated with the nickel-phosphine hydrogenase of DuBois et. al.We will enhance the hydrogenase activity of the catalyst by designing protein scaffolds that incorporate proton relays and systematicallymore » modulate the local environment of the catalyticcenter. In collaboration with DuBois and Shaw, the designs will be experimentally synthesized and characterized.« less

SPLINTS: small-molecule protein ligand interface stabilizers.

PubMed

Fischer, Eric S; Park, Eunyoung; Eck, Michael J; Thomä, Nicolas H

2016-04-01

Regulatory protein-protein interactions are ubiquitous in biology, and small molecule protein-protein interaction inhibitors are an important focus in drug discovery. Remarkably little attention has been given to the opposite strategy-stabilization of protein-protein interactions, despite the fact that several well-known therapeutics act through this mechanism. From a structural perspective, we consider representative examples of small molecules that induce or stabilize the association of protein domains to inhibit, or alter, signaling for nuclear hormone, GTPase, kinase, phosphatase, and ubiquitin ligase pathways. These SPLINTS (small-molecule protein ligand interface stabilizers) drive interactions that are in some cases physiologically relevant, and in others entirely adventitious. The diverse structural mechanisms employed suggest approaches for a broader and systematic search for such compounds in drug discovery. Copyright © 2016 Elsevier Ltd. All rights reserved.

Selective small-molecule inhibitors as chemical tools to define the roles of matrix metalloproteinases in disease.

PubMed

Meisel, Jayda E; Chang, Mayland

2017-11-01

The focus of this article is to highlight novel inhibitors and current examples where the use of selective small-molecule inhibitors has been critical in defining the roles of matrix metalloproteinases (MMPs) in disease. Selective small-molecule inhibitors are surgical chemical tools that can inhibit the targeted enzyme; they are the method of choice to ascertain the roles of MMPs and complement studies with knockout animals. This strategy can identify targets for therapeutic development as exemplified by the use of selective small-molecule MMP inhibitors in diabetic wound healing, spinal cord injury, stroke, traumatic brain injury, cancer metastasis, and viral infection. This article is part of a Special Issue entitled: Matrix Metalloproteinases edited by Rafael Fridman. Copyright © 2017 Elsevier B.V. All rights reserved.

Visualization of molecular structures using HoloLens-based augmented reality

PubMed Central

Hoffman, MA; Provance, JB

2017-01-01

Biological molecules and biologically active small molecules are complex three dimensional structures. Current flat screen monitors are limited in their ability to convey the full three dimensional characteristics of these molecules. Augmented reality devices, including the Microsoft HoloLens, offer an immersive platform to change how we interact with molecular visualizations. We describe a process to incorporate the three dimensional structures of small molecules and complex proteins into the Microsoft HoloLens using aspirin and the human leukocyte antigen (HLA) as examples. Small molecular structures can be introduced into the HoloStudio application, which provides native support for rotating, resizing and performing other interactions with these molecules. Larger molecules can be imported through the Unity gaming development platform and then Microsoft Visual Developer. The processes described here can be modified to import a wide variety of molecular structures into augmented reality systems and improve our comprehension of complex structural features. PMID:28815109

Structures, electronic properties and reaction paths from Fe(CO)5 molecule to small Fe clusters

NASA Astrophysics Data System (ADS)

Li, Zhi; Zhao, Zhen

2018-04-01

The geometries, electrical characters and reaction paths from Fe(CO)5 molecule to small Fe clusters were investigated by using all-electron density functional theory. The results show that in the decomposition process of pentacarbonyl-iron, Fe(CO)5 molecule prefers to remove a carbon monoxide and adsorb another Fe(CO)5 molecule to produce nonacarbonyldiiron Fe2(CO)9 then Fe2(CO)9 gradually removes carbon monoxide to produce small Fe clusters. As It can be seen from the highest occupied molecule orbital-lowest unoccupied molecule orbital gap curves, the Fe(CO)n=3, and 5 and Fe2(CO)n=3, 7 and 9 intermediates have higher chemical stability than their neighbors. The local magnetic moment of the carbon monoxide is aligning anti-ferromagnetic. The effect of external magnetic field to the initial decomposition products of Fe(CO)5 can be ignored.

Directed Chemical Evolution with an Outsized Genetic Code

PubMed Central

Krusemark, Casey J.; Tilmans, Nicolas P.; Brown, Patrick O.; Harbury, Pehr B.

2016-01-01

The first demonstration that macromolecules could be evolved in a test tube was reported twenty-five years ago. That breakthrough meant that billions of years of chance discovery and refinement could be compressed into a few weeks, and provided a powerful tool that now dominates all aspects of protein engineering. A challenge has been to extend this scientific advance into synthetic chemical space: to enable the directed evolution of abiotic molecules. The problem has been tackled in many ways. These include expanding the natural genetic code to include unnatural amino acids, engineering polyketide and polypeptide synthases to produce novel products, and tagging combinatorial chemistry libraries with DNA. Importantly, there is still no small-molecule analog of directed protein evolution, i.e. a substantiated approach for optimizing complex (≥ 10^9 diversity) populations of synthetic small molecules over successive generations. We present a key advance towards this goal: a tool for genetically-programmed synthesis of small-molecule libraries from large chemical alphabets. The approach accommodates alphabets that are one to two orders of magnitude larger than any in Nature, and facilitates evolution within the chemical spaces they create. This is critical for small molecules, which are built up from numerous and highly varied chemical fragments. We report a proof-of-concept chemical evolution experiment utilizing an outsized genetic code, and demonstrate that fitness traits can be passed from an initial small-molecule population through to the great-grandchildren of that population. The results establish the practical feasibility of engineering synthetic small molecules through accelerated evolution. PMID:27508294

Metathesis depolymerizable surfactants

DOEpatents

Jamison, Gregory M [Albuquerque, NM; Wheeler, David R [Albuquerque, NM; Loy, Douglas A [Tucson, AZ; Simmons, Blake A [San Francisco, CA; Long, Timothy M [Evanston, IL; McElhanon, James R [Manteca, CA; Rahimian, Kamyar [Albuquerque, NM; Staiger, Chad L [Albuquerque, NM

2008-04-15

A class of surfactant molecules whose structure includes regularly spaced unsaturation in the tail group and thus, can be readily decomposed by ring-closing metathesis, and particularly by the action of a transition metal catalyst, to form small molecule products. These small molecules are designed to have increased volatility and/or enhanced solubility as compared to the original surfactant molecule and are thus easily removed by solvent extraction or vacuum extraction at low temperature. By producing easily removable decomposition products, the surfactant molecules become particularly desirable as template structures for preparing meso- and microstructural materials with tailored properties.

Concentration-related response potentiometric titrations to study the interaction of small molecules with large biomolecules.

PubMed

Hamidi-Asl, Ezat; Daems, Devin; De Wael, Karolien; Van Camp, Guy; Nagels, Luc J

2014-12-16

In the present paper, the utility of a special potentiometric titration approach for recognition and calculation of biomolecule/small-molecule interactions is reported. This approach is fast, sensitive, reproducible, and inexpensive in comparison to the other methods for the determination of the association constant values (Ka) and the interaction energies (ΔG). The potentiometric titration measurement is based on the use of a classical polymeric membrane indicator electrode in a solution of the small-molecule ligand. The biomolecule is used as a titrant. The potential is measured versus a reference electrode and transformed into a concentration-related signal over the entire concentration interval, also at low concentrations, where the millivolt (y-axis) versus log canalyte (x-axis) potentiometric calibration curve is not linear. In the procedure, Ka is calculated for the interaction of cocaine with a cocaine binding aptamer and with an anticocaine antibody. To study the selectivity and cross-reactivity, other oligonucleotides and aptamers are tested, as well as other small ligand molecules such as tetrakis(4-chlorophenyl)borate, metergoline, lidocaine, and bromhexine. The calculated Ka compared favorably to the value reported in the literature using surface plasmon resonance. The potentiometric titration approach called "concentration-related response potentiometry" is used to study molecular interaction for seven macromolecular target molecules and four small-molecule ligands.

Challenges and Opportunities for Small-Molecule Fluorescent Probes in Redox Biology Applications.

PubMed

Jiang, Xiqian; Wang, Lingfei; Carroll, Shaina L; Chen, Jianwei; Wang, Meng C; Wang, Jin

2018-02-16

The concentrations of reactive oxygen/nitrogen species (ROS/RNS) are critical to various biochemical processes. Small-molecule fluorescent probes have been widely used to detect and/or quantify ROS/RNS in many redox biology studies and serve as an important complementary to protein-based sensors with unique applications. Recent Advances: New sensing reactions have emerged in probe development, allowing more selective and quantitative detection of ROS/RNS, especially in live cells. Improvements have been made in sensing reactions, fluorophores, and bioavailability of probe molecules. In this review, we will not only summarize redox-related small-molecule fluorescent probes but also lay out the challenges of designing probes to help redox biologists independently evaluate the quality of reported small-molecule fluorescent probes, especially in the chemistry literature. We specifically highlight the advantages of reversibility in sensing reactions and its applications in ratiometric probe design for quantitative measurements in living cells. In addition, we compare the advantages and disadvantages of small-molecule probes and protein-based probes. The low physiological relevant concentrations of most ROS/RNS call for new sensing reactions with better selectivity, kinetics, and reversibility; fluorophores with high quantum yield, wide wavelength coverage, and Stokes shifts; and structural design with good aqueous solubility, membrane permeability, low protein interference, and organelle specificity. Antioxid. Redox Signal. 00, 000-000.

Design strategy for photoinduced electron transfer-based small-molecule fluorescent probes of biomacromolecules.

PubMed

Zhang, Wei; Ma, Zhao; Du, Lupei; Li, Minyong

2014-06-07

As the cardinal support of innumerable biological processes, biomacromolecules such as proteins, nucleic acids and polysaccharides are of importance to living systems. The key to understanding biological processes is to realize the role of these biomacromolecules in thte localization, distribution, conformation and interaction with other molecules. With the current development and adaptation of fluorescent technologies in biomedical and pharmaceutical fields, the fluorescence imaging (FLI) approach of using small-molecule fluorescent probes is becoming an up-to-the-minute method for the detection and monitoring of these imperative biomolecules in life sciences. However, conventional small-molecule fluorescent probes may provide undesirable results because of their intrinsic deficiencies such as low signal-to-noise ratio (SNR) and false-positive errors. Recently, small-molecule fluorescent probes with a photoinduced electron transfer (PET) "on/off" switch for biomacromolecules have been thoroughly considered. When recognized by the biomacromolecules, these probes turn on/off the PET switch and change the fluorescence intensity to present a high SNR result. It should be emphasized that these PET-based fluorescent probes could be advantageous for understanding the pathogenesis of various diseases caused by abnormal expression of biomacromolecules. The discussion of this successful strategy involved in this review will be a valuable guide for the further development of new PET-based small-molecule fluorescent probes for biomacromolecules.

Inhibition of HIF-2.alpha. heterodimerization with HIF1.beta. (ARNT)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bruick, Richard K.; Caldwell, Charles G.; Frantz, Doug E.

2017-09-12

Provided is a method of inhibiting heterodimerization of HIF-2.alpha. to HIF1.beta. (ARNT) comprising binding certain small molecules to the HIF-2.alpha. PAS-B domain cavity but not to HIF1.alpha. and inhibiting HIF-2.alpha. heterodimerization to HIF1.beta. (ARNT) but not inhibiting HIF1.alpha. heterodimerization to HIF1.beta. (ARNT). Those certain small molecules are also referenced synonymously as HIF2-HDI and HIF2.alpha. heterodimerization inhibitors and also simply as certain small molecules.

Fullerene-free small molecule organic solar cells with a high open circuit voltage of 1.15 V.

PubMed

Ni, Wang; Li, Miaomiao; Kan, Bin; Liu, Feng; Wan, Xiangjian; Zhang, Qian; Zhang, Hongtao; Russell, Thomas P; Chen, Yongsheng

2016-01-11

A new small molecule named DTBTF with thiobarbituric acid as a terminal group was designed and synthesized as an acceptor for organic photovoltaic applications. DTBTF exhibits strong absorption in the visible region, and a relatively high lying LUMO energy level (-3.62 eV). All-small-molecule organic solar cells based on DR3TSBDT:DTBTF blend films show a considerable PCE of 3.84% with a high V(oc) of 1.15 V.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

The following are reported: theoretical calculations (configuration interaction, relativistic effective core potentials, polyatomics, CASSCF); proposed theoretical studies (clusters of Cu, Ag, Au, Ni, Pt, Pd, Rh, Ir, Os, Ru; transition metal cluster ions; transition metal carbide clusters; bimetallic mixed transition metal clusters); reactivity studies on transition metal clusters (reactivity with H{sub 2}, C{sub 2}H{sub 4}, hydrocarbons; NO and CO chemisorption on surfaces). Computer facilities and codes to be used, are described. 192 refs, 13 figs.

Photodissociation Studies of Polyatomic Free Radicals

DTIC Science & Technology

1993-08-01

photofragment, that varies with vibrational level, and appears to have a strong J dependence. We are currently in the process of modelling these effects, as well...have also begun to study the photodissociation dynamics of thionyl halides, The photodissociation of thionyl chloride (C12SO) is of interest as a model ...concerted three-body fragmentation mechanism as the primary dissociation channel. A Franck- Condon/golden rule model elucidates the geometry prior to

A size selective porous silicon grating-coupled Bloch surface and sub-surface wave biosensor.

PubMed

Rodriguez, Gilberto A; Ryckman, Judson D; Jiao, Yang; Weiss, Sharon M

2014-03-15

A porous silicon (PSi) grating-coupled Bloch surface and sub-surface wave (BSW/BSSW) biosensor is demonstrated to size selectively detect the presence of both large and small molecules. The BSW is used to sense large immobilized analytes at the surface of the structure while the BSSW that is confined inside but near the top of the structure is used to sensitively detect small molecules. Functionality of the BSW and BSSW modes is theoretically described by dispersion relations, field confinements, and simulated refractive index shifts within the structure. The theoretical results are experimentally verified by detecting two different small chemical molecules and one large 40 base DNA oligonucleotide. The PSi-BSW/BSSW structure is benchmarked against current porous silicon technology and is shown to have a 6-fold higher sensitivity in detecting large molecules and a 33% improvement in detecting small molecules. This is the first report of a grating-coupled BSW biosensor and the first report of a BSSW propagating mode. © 2013 Published by Elsevier B.V.

[Innovative application of small molecules to influence -pathogenicity of dental plaque].

PubMed

Janus, M M; Volgenant, C M C; Krom, B P

2018-05-01

Current preventive measures against infectious oral diseases are mainly focussed on plaque removal and promoting a healthy lifestyle. This in vitro study investigated a third preventive method: maintaining healthy dental plaque with the use of small molecules. As a model of dental plaque, in vitro biofilms were cultivated under conditions that induce pathogenic characteristics. The effect of erythritol and other small molecules on the pathogenic characteristics and bacterial composition of the biofilm was evaluated. The artificial sweetener erythritol and the molecule 3-Oxo-N-(2-oxycyclohexyl)dodecanamide (3-Oxo-N) had no clinically relevant effect on total biofilm formation. Erythritol did, however, lower the gingivitis related protease activity of the biofilm, while 3-Oxo-N blocked the caries related lactic acid accumulation. Furthermore, both substances ensured the biofilm maintained a young, non-pathogenic microbial composition. This shows it is possible to influence the dental plaque in a positive manner in vitro with the help of small molecules. Further research is necessary before this manipulation of dental plaque can be applied.

A Prospective Method to Guide Small Molecule Drug Design

ERIC Educational Resources Information Center

Johnson, Alan T.

2015-01-01

At present, small molecule drug design follows a retrospective path when considering what analogs are to be made around a current hit or lead molecule with the focus often on identifying a compound with higher intrinsic potency. What this approach overlooks is the simultaneous need to also improve the physicochemical (PC) and pharmacokinetic (PK)…

A New Scaling Law of Resonance in Total Scattering Cross Section in Gases

NASA Astrophysics Data System (ADS)

Raju, Gorur Govinda

2009-10-01

Electrical discharges in gases continue to be an active area of research because of industrial applications such as power systems, environmental clean up, laser technology, semiconductor fabrication etc. A fundamental knowledge of electron-gas neutral interaction is indispensable and, the total scattering cross section is one of the quantities that have been measured extensively. The energy dependence of the total cross sections shows peaks or resonance processes that are operative in the collision process. These peaks and the energies at which they occur are shown to satisfy a broad relationship involving the polarizability and the dipole moment of the target particle. Data on 62 target particles belonging to the following species are analyzed. (Eq 1) Rare gas atoms (Eq 2) Di-atomic molecules with combinations of polar, non-polar, attaching, and non-attaching properties Poly-atomic molecules with combinations of polar, non-polar, attaching, and non-attaching properties. Methods of improving the newly identified scaling law and possible application have been identified. 1 INTRODUCTION: Data on electron-neutral interactions are one of the most fundamental in the study of gaseous electronics and an immense literature, both experimental and theoretical, has become available since about the year 1920. [1-5]. In view of the central role which these data play in all facets of gas discharges and plasma science, it is felt that a critical review of available data is timely, mainly for the community of high voltage engineers and industries connected with plasma science in general. The electron-neutral interaction, often referred to as scattering in the scientific literature, is quantified by using the quantity called the total scattering cross section (QT, m^2). In the literature on cross section, total cross section and total scattering cross section are terms used synonymously and we follow the same practice. A definition may be found in reference [1]. This paper concerns scaling of total cross section of gases at resonance energy and the electron energy at which resonance occurs. The meaning of resonance is briefly explained in the following section. Here, we use the term scaling to relate the two quantities mentioned, namely, the resonance energy and the total cross section at that energy. Consistent with the definition of scaling, if the law proposed holds, one of the two quantities mentioned above may be calculated if the other is known. Such a method is very useful in gas discharge modeling and calculation of breakdown voltages, as more fully explained in the later section of the paper. 2 DESCRIPTION OF RESONANCE: A brief description of resonance phenomena in several types of target particles, viz., atomic, poly atomic, polar, non-polar phenomena are presented. 3 PREVIOUS SCALING LAWS: A common representation of a given characteristic with as few adjustable parameters as possible is generally known as the scaling law. The Paschen curve for breakdown voltage is such a familiar scaling law. With reference to cross sections several attempts have been made to obtain a scaling law, with varying degree of success. If the cross section-energy curve is qualitatively similar without having sharp peaks and oscillations, moderately successful scaling laws may be devised. For example, the ionization cross section- energy curves for most gases follow a general pattern. Several published scaling laws are discussed. 4 A NEW SCALING LAW AND DISCUSSION: In this work the author has compiled the resonance details for more than 60 gasest hat include the range from simple atoms to complex molecules that are polyatomic, dipolar, electron-attaching and isomers. The target particles exhibit a number of distinct features, as far as their total cross section variation with electron energy is concerned as already explained.

Demonstration of sub-femtomole sensitivity for small molecules with microsphere ring resonator sensors

NASA Astrophysics Data System (ADS)

White, Ian M.; Oveys, Hesam; Fan, Xudong

2006-02-01

Optical microsphere resonators can function as highly sensitive bio/chemical sensors due to the large Q-factor, which leads to high light-matter interaction. The whispering gallery modes (WGM) arise at the surface of the microsphere, creating a highly enhanced optical field that interacts with matter on or near the microsphere surface. As a result, the spectral position of the WGM is extremely sensitive to refractive index changes near the surface, such as when bio/chemical molecules bind to the sphere. We show the potential feasibility of a microsphere ring resonator as a sensor for small molecules by demonstrating detection of sub-femtomole changes in SiO II molecules at the surface of the microsphere. In this experiment, the silica molecules act as an excellent model for small molecule analytes because of their 60 Dalton molecular weight, and because we know nearly the exact quantity of molecules at the surface, which enables a sensitivity characterization. We measure the spectral shifts in the WGMs when low concentrations of hydrofluoric acid (HF) are added to a solution that is being probed by the microsphere. As the HF molecules break apart the SiO II molecules at the sphere surface, the WGMs shift due to the sub-nano-scale decrease in the size of the microsphere. These calculations show that the sensitivity of this microsphere resonator is on the order of 500 attomoles. Our results will lead to the utilization of optical microspheres for detection of trace quantities of small molecules for such applications as drug discovery, environmental monitoring, and enzyme detection using peptide cleavage.

Small Molecule Targeted Recruitment of a Nuclease to RNA.

PubMed

Costales, Matthew G; Matsumoto, Yasumasa; Velagapudi, Sai Pradeep; Disney, Matthew D

2018-06-06

The choreography between RNA synthesis and degradation is a key determinant in biology. Engineered systems such as CRISPR have been developed to rid a cell of RNAs. Here, we show that a small molecule can recruit a nuclease to a specific transcript, triggering its destruction. A small molecule that selectively binds the oncogenic microRNA(miR)-96 hairpin precursor was appended with a short 2'-5' poly(A) oligonucleotide. The conjugate locally activated endogenous, latent ribonuclease (RNase L), which selectively cleaved the miR-96 precursor in cancer cells in a catalytic and sub-stoichiometric fashion. Silencing miR-96 derepressed pro-apoptotic FOXO1 transcription factor, triggering apoptosis in breast cancer, but not healthy breast, cells. These results demonstrate that small molecules can be programmed to selectively cleave RNA via nuclease recruitment and has broad implications.

Small-molecule control of protein function through Staudinger reduction

NASA Astrophysics Data System (ADS)

Luo, Ji; Liu, Qingyang; Morihiro, Kunihiko; Deiters, Alexander

2016-11-01

Using small molecules to control the function of proteins in live cells with complete specificity is highly desirable, but challenging. Here we report a small-molecule switch that can be used to control protein activity. The approach uses a phosphine-mediated Staudinger reduction to activate protein function. Genetic encoding of an ortho-azidobenzyloxycarbonyl amino acid using a pyrrolysyl transfer RNA synthetase/tRNACUA pair in mammalian cells enables the site-specific introduction of a small-molecule-removable protecting group into the protein of interest. Strategic placement of this group renders the protein inactive until deprotection through a bioorthogonal Staudinger reduction delivers the active wild-type protein. This developed methodology was applied to the conditional control of several cellular processes, including bioluminescence (luciferase), fluorescence (enhanced green fluorescent protein), protein translocation (nuclear localization sequence), DNA recombination (Cre) and gene editing (Cas9).

RISC-Target Interaction: Cleavage and Translational Suppression

PubMed Central

van den Berg, Arjen; Mols, Johann; Han, Jiahuai

2008-01-01

Summary Small RNA molecules have been known and utilized to suppress gene expression for more than a decade. The discovery that these small RNA molecules are endogenously expressed in many organisms and have a critical role in controlling gene expression have led to the arising of a whole new field of research. Termed small interfering RNA (siRNA) or microRNA (miRNA) these ~22 nt RNA molecules have the capability to suppress gene expression through various mechanisms once they are incorporated in the multi-protein RNA-Induced Silencing Complex (RISC) and interact with their target mRNA. This review introduces siRNAs and microRNAs in a historical perspective and focuses on the key molecules in RISC, structural properties and mechanisms underlying the process of small RNA regulated post-transcriptional suppression of gene expression. PMID:18692607

Inkjet-Printed Small-Molecule Organic Light-Emitting Diodes: Halogen-Free Inks, Printing Optimization, and Large-Area Patterning.

PubMed

Zhou, Lu; Yang, Lei; Yu, Mengjie; Jiang, Yi; Liu, Cheng-Fang; Lai, Wen-Yong; Huang, Wei

2017-11-22

Manufacturing small-molecule organic light-emitting diodes (OLEDs) via inkjet printing is rather attractive for realizing high-efficiency and long-life-span devices, yet it is challenging. In this paper, we present our efforts on systematical investigation and optimization of the ink properties and the printing process to enable facile inkjet printing of conjugated light-emitting small molecules. Various factors on influencing the inkjet-printed film quality during the droplet generation, the ink spreading on the substrates, and its solidification processes have been systematically investigated and optimized. Consequently, halogen-free inks have been developed and large-area patterning inkjet printing on flexible substrates with efficient blue emission has been successfully demonstrated. Moreover, OLEDs manufactured by inkjet printing the light-emitting small molecules manifested superior performance as compared with their corresponding spin-cast counterparts.

Biased and unbiased strategies to identify biologically active small molecules.

PubMed

Abet, Valentina; Mariani, Angelica; Truscott, Fiona R; Britton, Sébastien; Rodriguez, Raphaël

2014-08-15

Small molecules are central players in chemical biology studies. They promote the perturbation of cellular processes underlying diseases and enable the identification of biological targets that can be validated for therapeutic intervention. Small molecules have been shown to accurately tune a single function of pluripotent proteins in a reversible manner with exceptional temporal resolution. The identification of molecular probes and drugs remains a worthy challenge that can be addressed by the use of biased and unbiased strategies. Hypothesis-driven methodologies employs a known biological target to synthesize complementary hits while discovery-driven strategies offer the additional means of identifying previously unanticipated biological targets. This review article provides a general overview of recent synthetic frameworks that gave rise to an impressive arsenal of biologically active small molecules with unprecedented cellular mechanisms. Copyright © 2014. Published by Elsevier Ltd.

Screening small-molecule compound microarrays for protein ligands without fluorescence labeling with a high-throughput scanning microscope.

PubMed

Fei, Yiyan; Landry, James P; Sun, Yungshin; Zhu, Xiangdong; Wang, Xiaobing; Luo, Juntao; Wu, Chun-Yi; Lam, Kit S

2010-01-01

We describe a high-throughput scanning optical microscope for detecting small-molecule compound microarrays on functionalized glass slides. It is based on measurements of oblique-incidence reflectivity difference and employs a combination of a y-scan galvometer mirror and an x-scan translation stage with an effective field of view of 2 cm x 4 cm. Such a field of view can accommodate a printed small-molecule compound microarray with as many as 10,000 to 20,000 targets. The scanning microscope is capable of measuring kinetics as well as endpoints of protein-ligand reactions simultaneously. We present the experimental results on solution-phase protein reactions with small-molecule compound microarrays synthesized from one-bead, one-compound combinatorial chemistry and immobilized on a streptavidin-functionalized glass slide.

Screening small-molecule compound microarrays for protein ligands without fluorescence labeling with a high-throughput scanning microscope

PubMed Central

Fei, Yiyan; Landry, James P.; Sun, Yungshin; Zhu, Xiangdong; Wang, Xiaobing; Luo, Juntao; Wu, Chun-Yi; Lam, Kit S.

2010-01-01

We describe a high-throughput scanning optical microscope for detecting small-molecule compound microarrays on functionalized glass slides. It is based on measurements of oblique-incidence reflectivity difference and employs a combination of a y-scan galvometer mirror and an x-scan translation stage with an effective field of view of 2 cm×4 cm. Such a field of view can accommodate a printed small-molecule compound microarray with as many as 10,000 to 20,000 targets. The scanning microscope is capable of measuring kinetics as well as endpoints of protein-ligand reactions simultaneously. We present the experimental results on solution-phase protein reactions with small-molecule compound microarrays synthesized from one-bead, one-compound combinatorial chemistry and immobilized on a streptavidin-functionalized glass slide. PMID:20210464

Synthetic Small Molecule Inhibitors of Hh Signaling As Anti-Cancer Chemotherapeutics

PubMed Central

Maschinot, C.A.; Pace, J.R.; Hadden, M.K.

2016-01-01

The hedgehog (Hh) pathway is a developmental signaling pathway that is essential to the proper embryonic development of many vertebrate systems. Dysregulation of Hh signaling has been implicated as a causative factor in the development and progression of several forms of human cancer. As such, the development of small molecule inhibitors of Hh signaling as potential anti-cancer chemotherapeutics has been a major area of research interest in both academics and industry over the past ten years. Through these efforts, synthetic small molecules that target multiple components of the Hh pathway have been identified and advanced to preclinical or clinical development. The goal of this review is to provide an update on the current status of several synthetic small molecule Hh pathway inhibitors and explore the potential of several recently disclosed inhibitory scaffolds. PMID:26310919

New Small Molecule Agonists to the Thyrotropin Receptor

PubMed Central

Ali, M. Rejwan; Ma, Risheng; David, Martine; Morshed, Syed A.; Ohlmeyer, Michael; Felsenfeld, Dan P.; Lau, Zerlina; Mezei, Mihaly; Davies, Terry F.

2015-01-01

Background Novel small molecular ligands (SMLs) to the thyrotropin receptor (TSHR) have potential as improved molecular probes and as therapeutic agents for the treatment of thyroid dysfunction and thyroid cancer. Methods To identify novel SMLs to the TSHR, we developed a transcription-based luciferase-cAMP high-throughput screening system and we screened 48,224 compounds from a 100K library in duplicate. Results We obtained 62 hits using the cut-off criteria of the mean±three standard deviations above the baseline. Twenty molecules with the greatest activity were rescreened against the parent CHO-luciferase cell for nonspecific activation, and we selected two molecules (MS437 and MS438) with the highest potency for further study. These lead molecules demonstrated no detectible cross-reactivity with homologous receptors when tested against luteinizing hormone (LH)/human chorionic gonadotropin receptor and follicle stimulating hormone receptor–expressing cells. Molecule MS437 had a TSHR-stimulating potency with an EC50 of 13×10−8 M, and molecule MS438 had an EC50 of 5.3×10−8 M. The ability of these small molecule agonists to bind to the transmembrane domain of the receptor and initiate signal transduction was suggested by their activation of a chimeric receptor consisting of an LHR ectodomain and a TSHR transmembrane. Molecular modeling demonstrated that these molecules bound to residues S505 and E506 for MS438 and T501 for MS437 in the intrahelical region of transmembrane helix 3. We also examined the G protein activating ability of these molecules using CHO cells co-expressing TSHRs transfected with luciferase reporter vectors in order to measure Gsα, Gβγ, Gαq, and Gα12 activation quantitatively. The MS437 and MS438 molecules showed potent activation of Gsα, Gαq, and Gα12 similar to TSH, but neither the small molecule agonists nor TSH showed activation of the Gβγ pathway. The small molecules MS437 and MS438 also showed upregulation of thyroglobulin (Tg), sodium iodine symporter (NIS), and TSHR gene expression. Conclusions Pharmacokinetic analysis of MS437 and MS438 indicated their pharmacotherapeutic potential, and their intraperitoneal administration to normal female mice resulted in significantly increased serum thyroxine levels, which could be maintained by repeated treatments. These molecules can therefore serve as lead molecules for further development of powerful TSH agonists. PMID:25333622

Targeting RNA in mammalian systems with small molecules.

PubMed

Donlic, Anita; Hargrove, Amanda E

2018-05-03

The recognition of RNA functions beyond canonical protein synthesis has challenged the central dogma of molecular biology. Indeed, RNA is now known to directly regulate many important cellular processes, including transcription, splicing, translation, and epigenetic modifications. The misregulation of these processes in disease has led to an appreciation of RNA as a therapeutic target. This potential was first recognized in bacteria and viruses, but discoveries of new RNA classes following the sequencing of the human genome have invigorated exploration of its disease-related functions in mammals. As stable structure formation is evolving as a hallmark of mammalian RNAs, the prospect of utilizing small molecules to specifically probe the function of RNA structural domains and their interactions is gaining increased recognition. To date, researchers have discovered bioactive small molecules that modulate phenotypes by binding to expanded repeats, microRNAs, G-quadruplex structures, and RNA splice sites in neurological disorders, cancers, and other diseases. The lessons learned from achieving these successes both call for additional studies and encourage exploration of the plethora of mammalian RNAs whose precise mechanisms of action remain to be elucidated. Efforts toward understanding fundamental principles of small molecule-RNA recognition combined with advances in methodology development should pave the way toward targeting emerging RNA classes such as long noncoding RNAs. Together, these endeavors can unlock the full potential of small molecule-based probing of RNA-regulated processes and enable us to discover new biology and underexplored avenues for therapeutic intervention in human disease. This article is categorized under: RNA Methods > RNA Analyses In Vitro and In Silico RNA Interactions with Proteins and Other Molecules > Small Molecule-RNA Interactions RNA in Disease and Development > RNA in Disease. © 2018 Wiley Periodicals, Inc.

Improving Photoconductance of Fluorinated Donors with Fluorinated Acceptors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Garner, Logan E.; Larson, Bryon; Oosterhout, Stefan

2016-11-21

This work investigates the influence of fluorination of both donor and acceptor materials on the generation of free charge carriers in small molecule donor/fullerene acceptor BHJ OPV active layers. A fluorinated and non-fluorinated small molecule analogue were synthesized and their optoelectronic properties characterized. The intrinsic photoconductance of blends of these small molecule donors was investigated using time-resolved microwave conductivity. Blends of the two donor molecules with a traditional non-fluorinated fullerene (PC70BM) as well as a fluorinated fullerene (C60(CF3)2-1) were investigated using 5% and 50% fullerene loading. We demonstrate for the first time that photoconductance in a 50:50 donor:acceptor BHJ blendmore » using a fluorinated fullerene can actually be improved relative to a traditional non-fluorinated fullerene by fluorinating the donor molecule as well.« less

Comparison of small molecules and oligonucleotides that target a toxic, non-coding RNA.

PubMed

Costales, Matthew G; Rzuczek, Suzanne G; Disney, Matthew D

2016-06-01

Potential RNA targets for chemical probes and therapeutic modalities are pervasive in the transcriptome. Oligonucleotide-based therapeutics are commonly used to target RNA sequence. Small molecules are emerging as a modality to target RNA structures selectively, but their development is still in its infancy. In this work, we compare the activity of oligonucleotides and several classes of small molecules that target the non-coding r(CCUG) repeat expansion (r(CCUG)(exp)) that causes myotonic dystrophy type 2 (DM2), an incurable disease that is the second-most common cause of adult onset muscular dystrophy. Small molecule types investigated include monomers, dimers, and multivalent compounds synthesized on-site by using RNA-templated click chemistry. Oligonucleotides investigated include phosphorothioates that cleave their target and vivo-morpholinos that modulate target RNA activity via binding. We show that compounds assembled on-site that recognize structure have the highest potencies amongst small molecules and are similar in potency to a vivo-morpholino modified oligonucleotide that targets sequence. These studies are likely to impact the design of therapeutic modalities targeting other repeats expansions that cause fragile X syndrome and amyotrophic lateral sclerosis, for example. Copyright © 2016. Published by Elsevier Ltd.

In Situ Oxidation Synthesis of p-Type Composite with Narrow-Bandgap Small Organic Molecule Coating on Single-Walled Carbon Nanotube: Flexible Film and Thermoelectric Performance.

PubMed

Gao, Caiyan; Chen, Guangming

2018-03-01

Although composites of organic polymers or n-type small molecule/carbon nanotube (CNT) have achieved significant advances in thermoelectric (TE) applications, p-type TE composites of small organic molecules as thick surface coating layers on the surfaces of inorganic nanoparticles still remain a great challenge. Taking advantage of in situ oxidation reaction of thieno[3,4-b]pyrazine (TP) into TP di-N-oxide (TPNO) on single-walled CNT (SWCNT) surface, a novel synthesis strategy is proposed to achieve flexible films of TE composites with narrow-bandgap (1.19 eV) small molecule coating on SWCNT surface. The TE performance can be effectively enhanced and conveniently tuned by poly(sodium-p-styrenesulfonate) content, TPNO/SWCNT mass ratio, and posttreatment by various polar solvents. The maximum of the composite power factor at room temperature is 29.4 ± 1.0 µW m -1 K -2 . The work presents a way to achieve flexible films of p-type small organic molecule/inorganic composites with clear surface coating morphology for TE application. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Measurement of Small Molecular Dopant F4TCNQ and C 60F 36 Diffusion in Organic Bilayer Architectures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Jun; Rochester, Chris W.; Jacobs, Ian E.

2015-12-03

The diffusion of molecules through and between organic layers is a serious stability concern in organic electronic devices. In this paper, the temperature-dependent diffusion of molecular dopants through small molecule hole transport layers is observed. Specifically we investigate bilayer stacks of small molecules used for hole transport (MeO-TPD) and p-type dopants (F4TCNQ and C 60F 36) used in hole injection layers for organic light emitting diodes and hole collection electrodes for organic photovoltaics. With the use of absorbance spectroscopy, photoluminescence spectroscopy, neutron reflectometry, and near-edge X-ray absorption fine structure spectroscopy, we are able to obtain a comprehensive picture of themore » diffusion of fluorinated small molecules through MeO-TPD layers. F4TCNQ spontaneously diffuses into the MeO-TPD material even at room temperature, while C 60F 36, a much bulkier molecule, is shown to have a substantially higher morphological stability. Finally, this study highlights that the differences in size/geometry and thermal properties of small molecular dopants can have a significant impact on their diffusion in organic device architectures.« less

A semantic web ontology for small molecules and their biological targets.

PubMed

Choi, Jooyoung; Davis, Melissa J; Newman, Andrew F; Ragan, Mark A

2010-05-24

A wide range of data on sequences, structures, pathways, and networks of genes and gene products is available for hypothesis testing and discovery in biological and biomedical research. However, data describing the physical, chemical, and biological properties of small molecules have not been well-integrated with these resources. Semantically rich representations of chemical data, combined with Semantic Web technologies, have the potential to enable the integration of small molecule and biomolecular data resources, expanding the scope and power of biomedical and pharmacological research. We employed the Semantic Web technologies Resource Description Framework (RDF) and Web Ontology Language (OWL) to generate a Small Molecule Ontology (SMO) that represents concepts and provides unique identifiers for biologically relevant properties of small molecules and their interactions with biomolecules, such as proteins. We instanced SMO using data from three public data sources, i.e., DrugBank, PubChem and UniProt, and converted to RDF triples. Evaluation of SMO by use of predetermined competency questions implemented as SPARQL queries demonstrated that data from chemical and biomolecular data sources were effectively represented and that useful knowledge can be extracted. These results illustrate the potential of Semantic Web technologies in chemical, biological, and pharmacological research and in drug discovery.

Small molecules as therapy for uveitis: a selected perspective of new and developing agents.

PubMed

Pleyer, Uwe; Algharably, Engi Abdel-Hady; Feist, Eugen; Kreutz, Reinhold

2017-09-01

Intraocular inflammation (uveitis) remains a significant burden of legal blindness. Because of its immune mediated and chronic recurrent nature, common therapy includes corticosteroids, disease-modifying anti-rheumatic drugs and more recently biologics as immune modulatory agents. The purpose of this article is to identify the role of new treatment approaches focusing on small molecules as therapeutic option in uveitis. Areas covered: A MEDLINE database search was conducted through February 2017 using the terms 'uveitis' and 'small molecule'. To provide ongoing and future perspectives in treatment options, also clinical trials as registered at ClinicalTrials.gov were included. Both, results from experimental as well as clinical research in this field were included. Since this field is rapidly evolving, a selection of promising agents had to be made. Expert opinion: Small molecules may interfere at different steps of the inflammatory cascade and appear as an interesting option in the treatment algorithm of uveitis. Because of their highly targeted molecular effects and their favorable bioavailability with the potential of topical application small molecules hold great promise. Nevertheless, a careful evaluation of these agents has to be made, since current experience is almost exclusively based on experimental uveitis models and few registered trials.

DBDA as a Novel Matrix for the Analyses of Small Molecules and Quantification of Fatty Acids by Negative Ion MALDI-TOF MS.

PubMed

Ling, Ling; Li, Ying; Wang, Sheng; Guo, Liming; Xiao, Chunsheng; Chen, Xuesi; Guo, Xinhua

2018-04-01

Matrix interference ions in low mass range has always been a concern when using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) to analyze small molecules (<500 Da). In this work, a novel matrix, N1,N4-dibenzylidenebenzene-1,4-diamine (DBDA) was synthesized for the analyses of small molecules by negative ion MALDI-TOF MS. Notably, only neat ions ([M-H] - ) of fatty acids without matrix interference appeared in the mass spectra and the limit of detection (LOD) reached 0.3 fmol. DBDA also has great performance towards other small molecules such as amino acids, peptides, and nucleotide. Furthermore, with this novel matrix, the free fatty acids in serum were quantitatively analyzed based on the correlation curves with correlation coefficient of 0.99. In addition, UV-Vis experiments and molecular orbital calculations were performed to explore mechanism about DBDA used as matrix in the negative ion mode. The present work shows that the DBDA matrix is a highly sensitive matrix with few interference ions for analysis of small molecules. Meanwhile, DBDA is able to precisely quantify the fatty acids in real biological samples. Graphical Abstract ᅟ.

SMA Spectral Line Survey of the Proto-Planetary Nebula CRL 618

NASA Astrophysics Data System (ADS)

Patel, Nimesh A.; Gottlieb, Carl; Young, Ken; Kaminski, Tomasz Tomek; McCarthy, Michael; Menten, Karl; Primiani, Rurik; Lee, Chin-Fei; Gupta, Harshal

2018-01-01

Carbon-rich Asymptotic Giant Branch (AGB) stars are major sources of gas and dust in the interstellar medium. AGB stars remain in their evolutionary stage for 1 to 10 Myrs, during which they have very high mass loss rates that increase at the end. During the brief (~1000 yr) period in the evolution from the AGB to the Planetary Nebula (PN) stage there are dramatic changes in the morphology from nearly spherical symmetry, to bipolar, quadrupolar and more complex structures, with the development of both slow and fast (100 km/s) outflows. The molecular composition of these objects' cirumstellar envelopes also evolves from being similar to that of parent AGB star (mainly diatomic and small polyatomic species), to more complex molecules (including ions).We have started an observational study of a sample of Proto-Planetary nebulae (PPN) with the Submillimeter Array to carry out spectral-line surveys of ~60 GHz frequency coverage in the 345 GHz band (similar to our published IRC+10216 line survey of 2011). Here we present preliminary results from the line survey of the carbon-rich PPN CRL 618, covering a frequency range of 281.9 to 359.4 GHz. Observations were carried out in January 2016 and September 2017, with the SMA in compact (3" angular resolution) and very extended (0.5") configurations, respectively.More than 1100 lines were detected in CRL 618. The majority of them can be attributed to HC3N and c-C3H2, and their isotopologues. About 350 lines are as yet unassigned. The continuum emission is unresolved even at 0.5" resolution. Several hydrogen recombination lines are detected from the central HII region. Lines of CO, HCO+, CS show the fast outflow wings, while the majority of molecular emission arises from a compact region of about 1" diameter. We present LTEmodeling and rotation temperature diagram analysis of HC3N, c-C3H2, CH3CN, and their isotopologues. We plan to observe another PPN, CRL 2688 with the SMA in 2018. Together, these imaging line surveys will provide observational constraints on models of the chemical evolution from AGB stars to Planetary Nebulae.

Exporters for Production of Amino Acids and Other Small Molecules.

PubMed

Eggeling, Lothar

Microbes are talented catalysts to synthesize valuable small molecules in their cytosol. However, to make full use of their skills - and that of metabolic engineers - the export of intracellularly synthesized molecules to the culture medium has to be considered. This step is as essential as is each step for the synthesis of the favorite molecule of the metabolic engineer, but is frequently not taken into account. To export small molecules via the microbial cell envelope, a range of different types of carrier proteins is recognized to be involved, which are primary active carriers, secondary active carriers, or proteins increasing diffusion. Relevant export may require just one carrier as is the case with L-lysine export by Corynebacterium glutamicum or involve up to four carriers as known for L-cysteine excretion by Escherichia coli. Meanwhile carriers for a number of small molecules of biotechnological interest are recognized, like for production of peptides, nucleosides, diamines, organic acids, or biofuels. In addition to carriers involved in amino acid excretion, such carriers and their impact on product formation are described, as well as the relatedness of export carriers which may serve as a hint to identify further carriers required to improve product formation by engineering export.

Remote Raman Efficiencies and Cross-Sections of Organic and Inorganic Chemicals.

PubMed

Acosta-Maeda, Tayro E; Misra, Anupam K; Porter, John N; Bates, David E; Sharma, Shiv K

2017-05-01

We determined Raman cross-sections of various organic liquids and inorganic polyatomic ions in aqueous solutions with a 532 nm pulsed laser using remote Raman systems developed at the University of Hawaii. Using a calibrated integrating sphere as a light source, we converted the intensity counts in the spectrum of the light from the integrating sphere measured with UH remote Raman instrument to spectral radiance. From these data, a response function of the remote Raman instrument was obtained. With the intensity-calibrated instrument, we collected remote Raman data from a standard 1 mm path length fused silica spectrophotometer cell filled with cyclohexane. The measured value of the differential Raman cross-section for the 801 cm -1 vibrational mode of cyclohexane is 4.55 × 10 -30 cm 2 sr -1 molecule -1 when excited by a 532 nm laser, in good agreement with the values reported in the literature. Using the measured cyclohexane Raman cross-section as a reference and relative Raman mode intensities of the various ions and organic liquids, we calculated the Raman cross-sections of the strongest Raman lines of nitrate, sulfate, carbonate, phosphate ions, and organic liquids by maintaining same experimental conditions for remote Raman detection. These relative Raman cross-section values will be useful for estimating detection capabilities of remote Raman systems for planetary exploration.

Mode-specific multi-channel dynamics of the F- + CHD2Cl reaction on a global ab initio potential energy surface

NASA Astrophysics Data System (ADS)

Szabó, István; Czakó, Gábor

2016-10-01

We report a detailed quasiclassical trajectory study for the dynamics of the ground-state and CH/CD stretching-excited F- + CHD2Cl(vCH/CD = 0, 1) → Cl- + CHD2F, HF + CD2Cl-, and DF + CHDCl- SN2, proton-, and deuteron-abstraction reactions using a full-dimensional global ab initio analytical potential energy surface. The simulations show that (a) CHD2Cl(vCH/CD = 1), especially for vCH = 1, maintains its mode-specific excited character prior to interaction, (b) the SN2 reaction is vibrationally mode-specific, (c) double inversion can occur and is enhanced upon CH/CD stretching excitations, (d) in the abstraction reactions the HF channel is preferred and the vCH/CD = 1 excitations significantly promote the HF/DF channels, (e) back-side rebound, back-side stripping, and front-side stripping are the dominant direct abstraction mechanisms based on correlated scattering- and attack-angle distributions, (f) the exact classical vibrational energy-based Gaussian binning (1GB) provides realistic mode-specific polyatomic product state distributions, (g) in the abstraction reactions CH and CD stretchings are not pure spectator modes and mainly ground-state products are produced, thus most of the initial energy transfers into product translation, and (h) the HF and DF product molecules are rotationally cold without any significant dependence on the reactant's and HF/DF vibrational states.

Computation of Electron Impact Ionization Cross sections of Iron Hydrogen Clusters - Relevance in Fusion Plasmas

NASA Astrophysics Data System (ADS)

Patel, Umang; Joshipura, K. N.

2017-04-01

Plasma-wall interaction (PWI) is one of the key issues in nuclear fusion research. In nuclear fusion devices, such as the JET tokamak or the ITER, first-wall materials will be directly exposed to plasma components. Erosion of first-wall materials is a consequence of the impact of hydrogen and its isotopes as main constituents of the hot plasma. Besides the formation of gas-phase atomic species in various charge states, di- and polyatomic molecular species are expected to be formed via PWI processes. These compounds may profoundly disturb the fusion plasma, may lead to unfavorable re-deposition of materials and composites in other areas of the vessel. Interaction between atoms, molecules as well transport of impurities are of interest for modelling of fusion plasma. Qion by electron impact are such process also important in low temperature plasma processing, astrophysics etc. We reported electron impact Qionfor iron hydrogen clusters, FeHn (n = 1 to 10) from ionization threshold to 2000 eV. A semi empirical approach called Complex Scattering Potential - Ionization Contribution (CSP-ic) has been employed for the reported calculation. In context of fusion relevant species Qion were reported for beryllium and its hydrides, tungsten and its oxides and cluster of beryllium-tungsten by Huber et al.. Iron hydrogen clusters are another such species whose Qion were calculated through DM and BEB formalisms, same has been compared with present calculations.

Reaction-based small-molecule fluorescent probes for dynamic detection of ROS and transient redox changes in living cells and small animals.

PubMed

Lü, Rui

2017-09-01

Dynamic detection of transient redox changes in living cells and animals has broad implications for human health and disease diagnosis, because intracellular redox homeostasis regulated by reactive oxygen species (ROS) plays important role in cell functions, normal physiological functions and some serious human diseases (e.g., cancer, Alzheimer's disease, diabetes, etc.) usually have close relationship with the intracellular redox status. Small-molecule ROS-responsive fluorescent probes can act as powerful tools for dynamic detection of ROS and redox changes in living cells and animals through fluorescence imaging techniques; and great advances have been achieved recently in the design and synthesis of small-molecule ROS-responsive fluorescent probes. This article highlights up-to-date achievements in designing and using the reaction-based small-molecule fluorescent probes (with high sensitivity and selectivity to ROS and redox cycles) in the dynamic detection of ROS and transient redox changes in living cells and animals through fluorescence imaging. Copyright © 2017. Published by Elsevier Ltd.

The Endoplasmic Reticulum Membrane Is Permeable to Small Molecules

PubMed Central

Le Gall, Sylvie; Neuhof, Andrea; Rapoport, Tom

2004-01-01

The lumen of the endoplasmic reticulum (ER) differs from the cytosol in its content of ions and other small molecules, but it is unclear whether the ER membrane is as impermeable as other membranes in the cell. Here, we have tested the permeability of the ER membrane to small, nonphysiological molecules. We report that isolated ER vesicles allow different chemical modification reagents to pass from the outside into the lumen with little hindrance. In permeabilized cells, the ER membrane allows the passage of a small, charged modification reagent that is unable to cross the plasma membrane or the lysosomal and trans-Golgi membranes. A larger polar reagent of ∼5 kDa is unable to pass through the ER membrane. Permeation of the small molecules is passive because it occurs at low temperature in the absence of energy. These data indicate that the ER membrane is significantly more leaky than other cellular membranes, a property that may be required for protein folding and other functions of the ER. PMID:14617815

Cucurbituril mediated single molecule detection and identification via recognition tunneling.

PubMed

Xiao, Bohuai; Liang, Feng; Liu, Simin; Im, JongOne; Li, Yunchuan; Liu, Jing; Zhang, Bintian; Zhou, Jianghao; He, Jin; Chang, Shuai

2018-06-08

Recognition tunneling (RT) is an emerging technique for investigating single molecules in a tunnel junction. We have previously demonstrated its capability of single molecule detection and identification, as well as probing the dynamics of intermolecular bonding at the single molecule level. Here by introducing cucurbituril as a new class of recognition molecule, we demonstrate a powerful platform for electronically investigating the host-guest chemistry at single molecule level. In this report, we first investigated the single molecule electrical properties of cucurbituril in a tunnel junction. Then we studied two model guest molecules, aminoferrocene and amantadine, which were encapsulated by cucurbituril. Small differences in conductance and lifetime can be recognized between the host-guest complexes with the inclusion of different guest molecules. By using a machine learning algorithm to classify the RT signals in a hyper dimensional space, the accuracy of guest molecule recognition can be significantly improved, suggesting the possibility of using cucurbituril molecule for single molecule identification. This work enables a new class of recognition molecule for RT technique and opens the door for detecting a vast variety of small molecules by electrical measurements.

Development of small molecule biosensors by coupling the recognition of the bacterial allosteric transcription factor with isothermal strand displacement amplification.

PubMed

Yao, Yongpeng; Li, Shanshan; Cao, Jiaqian; Liu, Weiwei; Fan, Keqiang; Xiang, Wensheng; Yang, Keqian; Kong, Deming; Wang, Weishan

2018-05-08

Here, we demonstrate an easy-to-implement and general biosensing strategy by coupling the small-molecule recognition of the bacterial allosteric transcription factor (aTF) with isothermal strand displacement amplification (SDA) in vitro. Based on this strategy, we developed two biosensors for the detection of an antiseptic, p-hydroxybenzoic acid, and a disease marker, uric acid, using bacterial aTF HosA and HucR, respectively, highlighting the great potential of this strategy for the development of small-molecule biosensors.

A structural biology perspective on bioactive small molecules and their plant targets.

PubMed

Kumari, Selva; van der Hoorn, Renier A L

2011-10-01

Structural biology efforts in recent years have generated numerous co-crystal structures of bioactive small molecules interacting with their plant targets. These studies include the targets of various phytohormones, pathogen-derived effectors, herbicides and other bioactive compounds. Here we discuss that this collection of structures contains excellent examples of nine collective observations: molecular glues, allostery, inhibitors, molecular mimicry, promiscuous binding sites, unexpected electron densities, natural selection at atomic resolution, and applications in structure-guided mutagenesis and small molecule design. Copyright © 2011 Elsevier Ltd. All rights reserved.

New developments in microbial interspecies signaling.

PubMed

Shank, Elizabeth Anne; Kolter, Roberto

2009-04-01

There is a growing appreciation that in addition to well-documented intraspecies quorum sensing systems, small molecules act as signals between microbes of different species. This review will focus on how bacterial small molecules modulate these interspecies interactions. We will particularly emphasize complex relationships such as those between microbes and insects, interactions resulting in non-antagonistic outcomes (i.e. developmental and morphological processes), how co-culture can lead to the discovery of new small molecules, and the use of known compounds to evoke unexpected responses and mediate crosstalk between microbes.

Tailoring the interface using thiophene small molecules in TiO2/P3HT hybrid solar cells.

PubMed

Freitas, Flavio S; Clifford, John N; Palomares, Emilio; Nogueira, Ana F

2012-09-14

In this paper we focus on the effect of carboxylated thiophene small molecules as interface modifiers in TiO(2)/P3HT hybrid solar cells. Our results show that small differences in the chemical structure of these molecules, for example, the presence of the -CH(2)- group in the 2-thiopheneacetic acid (TAA), can greatly increase the TiO(2) surface wettability, improving the TiO(2)/polymer contact. This effect is important to enhance exciton splitting and charge separation.

Janus Kinase Antagonists and Other Novel Small Molecules for the Treatment of Crohn's Disease.

PubMed

Boland, Brigid S; Vermeire, Séverine

2017-09-01

There is an ongoing, unmet need for effective therapies for Crohn's disease. Treatments for Crohn's disease continue to evolve from the traditional biologics to novel small molecules, with targeted mechanisms directed toward pathways that are dysregulated in Crohn's disease. There are multiple emerging mechanisms of action, including Janus kinase inhibition, Smad7 inhibition, and sphingosine-1-phosphate receptor modulators, that are administered as oral medications, and small molecules represent the next generation of therapies for Crohn's disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Theoretical Investigation of Single-Molecule Sensing Using Nanotube-Enhanced Circular Dichroism.

PubMed

Silva, Jaime; Milne, Bruce F; Nogueira, Fernando

2018-06-19

First-principles calculations have been used to investigate the potential use of circular dichroism (CD) spectroscopy in single-molecule sensing. Using a real-space implementation of time-dependent density functional theory (TDDFT), several systems involving single-walled carbon nanotubes (SWCNT) and small molecules have been studied to evaluate their CD response. Large induced CD (ICD) effects, differing for each test molecule, were observed in all SWCNT-molecule complexes. As the SWCNT used in this study shows no intrinsic CD response, the ICD spectra are the result of interaction with the small molecules. This finding is general and independent of the (a)chiral nature of the adsorbed molecule. Our results indicate that it is possible to design a system that uses SWCNT for detection of molecules using the change in CD spectrum of the system induced by adsorption of the molecule onto the SWCNT surface.

2016 White Paper on recent issues in bioanalysis: focus on biomarker assay validation (BAV) (Part 1 - small molecules, peptides and small molecule biomarkers by LCMS).

PubMed

Yang, Eric; Welink, Jan; Cape, Stephanie; Woolf, Eric; Sydor, Jens; James, Christopher; Goykhman, Dina; Arnold, Mark; Addock, Neil; Bauer, Ronald; Buonarati, Michael; Ciccimaro, Eugene; Dodda, Raj; Evans, Christopher; Garofolo, Fabio; Hughes, Nicola; Islam, Rafiq; Nehls, Corey; Wilson, Amanda; Briscoe, Chad; Bustard, Mark; Coppola, Laura; Croft, Stephanie; Drexler, Dieter; Ferrari, Luca; Fraier, Daniela; Jenkins, Rand; Kadavil, John; King, Lloyd; Li, Wenkui; Lima Santos, Gustavo Mendes; Musuku, Adrien; Ramanathan, Ragu; Saito, Yoshiro; Savoie, Natasha; Summerfield, Scott; Sun, Rachel; Tampal, Nilufer; Vinter, Steve; Wakelin-Smith, Jason; Yue, Qin

2016-10-07

The 2016 10 th Workshop on Recent Issues in Bioanalysis (10 th WRIB) took place in Orlando, Florida with participation of close to 700 professionals from pharmaceutical/biopharmaceutical companies, biotechnology companies, contract research organizations, and regulatory agencies worldwide. WRIB was once again a 5-day, weeklong event - A Full Immersion Week of Bioanalysis including Biomarkers and Immunogenicity. As usual, it was specifically designed to facilitate sharing, reviewing, discussing and agreeing on approaches to address the most current issues of interest including both small and large molecule analysis involving LCMS, hybrid LBA/LCMS, and LBA approaches, with the focus on biomarkers and immunogenicity. This 2016 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop, and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. This white paper is published in 3 parts due to length. This part (Part 1) discusses the recommendations for small molecules, peptides and small molecule biomarkers by LCMS. Part 2 (Hybrid LBA/LCMS and regulatory inputs from major global health authorities) and Part 3 (large molecule bioanalysis using LBA, biomarkers and immunogenicity) will be published in the Bioanalysis journal, issue 23.

Diffusion of small molecules into medaka embryos improved by electroporation

PubMed Central

2013-01-01

Background Diffusion of small molecules into fish embryos is essential for many experimental procedures in developmental biology and toxicology. Since we observed a weak uptake of lithium into medaka eggs we started a detailed analysis of its diffusion properties using small fluorescent molecules. Results Contrary to our expectations, not the rigid outer chorion but instead membrane systems surrounding the embryo/yolk turned out to be the limiting factor for diffusion into medaka eggs. The consequence is a bi-phasic uptake of small molecules first reaching the pervitelline space with a diffusion half-time in the range of a few minutes. This is followed by a slow second phase (half-time in the range of several hours) during which accumulation in the embryo/yolk takes place. Treatment with detergents improved the uptake, but strongly affected the internal distribution of the molecules. Testing electroporation we could establish conditions to overcome the diffusion barrier. Applying this method to lithium chloride we observed anterior truncations in medaka embryos in agreement with its proposed activation of Wnt signalling. Conclusions The diffusion of small molecules into medaka embryos is slow, caused by membrane systems underneath the chorion. These results have important implications for pharmacologic/toxicologic techniques like the fish embryo test, which therefore require extended incubation times in order to reach sufficient concentrations in the embryos. PMID:23815821

Small molecules targeting LapB protein prevent Listeria attachment to catfish muscle

PubMed Central

Das, Bhaskar; Lawrence, Mark

2017-01-01

Listeria monocytogenes is a Gram-positive foodborne pathogen and the causative agent of listeriosis. L. monocytogenes lapB gene encodes a cell wall surface anchor protein, and mutation of this gene causes Listeria attenuation in mice. In this work, the potential role of Listeria LapB protein in catfish fillet attachment was investigated. To achieve this, boron-based small molecules designed to interfere with the active site of the L. monocytogenes LapB protein were developed, and their ability to prevent L. monocytogenes attachment to fish fillet was tested. Results indicated that seven out of nine different small molecules were effective in reducing the Listeria attachment to catfish fillets. Of these, three small molecules (SM3, SM5, and SM7) were highly effective in blocking Listeria attachment to catfish fillets. This study suggests an alternative strategy for reduction of L. monocytogenes contamination in fresh and frozen fish products. PMID:29253892

Incorporation of ionic liquid into porous polymer monoliths to enhance the separation of small molecules in reversed-phase high-performance liquid chromatography.

PubMed

Wang, Jiafei; Bai, Ligai; Wei, Zhen; Qin, Junxiao; Ma, Yamin; Liu, Haiyan

2015-06-01

An ionic liquid was incorporated into the porous polymer monoliths to afford stationary phases with enhanced chromatographic performance for small molecules in reversed-phase high-performance liquid chromatography. The effect of the ionic liquid in the polymerization mixture on the performance of the monoliths was studied in detail. While monoliths without ionic liquid exhibited poor resolution and low efficiency, the addition of ionic liquid to the polymerization mixture provides highly increased resolution and high efficiency. The chromatographic performances of the monoliths were demonstrated by the separations of various small molecules including aromatic hydrocarbons, isomers, and homologues using a binary polar mobile phase. The present column efficiency reached 27 000 plates/m, which showed that the ionic liquid monoliths are alternative stationary phases in the separation of small molecules by high-performance liquid chromatography. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Precise small molecule recognition of a toxic CUG RNA repeat expansion

PubMed Central

Rzuczek, Suzanne G; Colgan, Lesley A; Nakai, Yoshio; Cameron, Michael D; Furling, Denis; Yasuda, Ryohei; Disney, Matthew D

2017-01-01

Excluding the ribosome and riboswitches, developing small molecules that selectively target RNA is a longstanding problem in chemical biology. A typical cellular RNA is difficult to target because it has little tertiary, but abundant secondary structure. We designed allele-selective compounds that target such an RNA, the toxic noncoding repeat expansion (r(CUG)exp) that causes myotonic dystrophy type 1 (DM1). We developed several strategies to generate allele-selective small molecules, including non-covalent binding, covalent binding, cleavage and on-site probe synthesis. Covalent binding and cleavage enabled target profiling in cells derived from individuals with DM1, showing precise recognition of r(CUG)exp. In the on-site probe synthesis approach, small molecules bound adjacent sites in r(CUG)exp and reacted to afford picomolar inhibitors via a proximity-based click reaction only in DM1-affected cells. We expanded this approach to image r(CUG)exp in its natural context. PMID:27941760

Precise small-molecule recognition of a toxic CUG RNA repeat expansion.

PubMed

Rzuczek, Suzanne G; Colgan, Lesley A; Nakai, Yoshio; Cameron, Michael D; Furling, Denis; Yasuda, Ryohei; Disney, Matthew D

2017-02-01

Excluding the ribosome and riboswitches, developing small molecules that selectively target RNA is a longstanding problem in chemical biology. A typical cellular RNA is difficult to target because it has little tertiary, but abundant secondary structure. We designed allele-selective compounds that target such an RNA, the toxic noncoding repeat expansion (r(CUG) exp ) that causes myotonic dystrophy type 1 (DM1). We developed several strategies to generate allele-selective small molecules, including non-covalent binding, covalent binding, cleavage and on-site probe synthesis. Covalent binding and cleavage enabled target profiling in cells derived from individuals with DM1, showing precise recognition of r(CUG) exp . In the on-site probe synthesis approach, small molecules bound adjacent sites in r(CUG) exp and reacted to afford picomolar inhibitors via a proximity-based click reaction only in DM1-affected cells. We expanded this approach to image r(CUG) exp in its natural context.

Small molecule alteration of RNA sequence in cells and animals.

PubMed

Guan, Lirui; Luo, Yiling; Ja, William W; Disney, Matthew D

2017-10-18

RNA regulation and maintenance are critical for proper cell function. Small molecules that specifically alter RNA sequence would be exceptionally useful as probes of RNA structure and function or as potential therapeutics. Here, we demonstrate a photochemical approach for altering the trinucleotide expanded repeat causative of myotonic muscular dystrophy type 1 (DM1), r(CUG) exp . The small molecule, 2H-4-Ru, binds to r(CUG) exp and converts guanosine residues to 8-oxo-7,8-dihydroguanosine upon photochemical irradiation. We demonstrate targeted modification upon irradiation in cell culture and in Drosophila larvae provided a diet containing 2H-4-Ru. Our results highlight a general chemical biology approach for altering RNA sequence in vivo by using small molecules and photochemistry. Furthermore, these studies show that addition of 8-oxo-G lesions into RNA 3' untranslated regions does not affect its steady state levels. Copyright © 2017 Elsevier Ltd. All rights reserved.

High-Throughput RT-PCR for small-molecule screening assays

PubMed Central

Bittker, Joshua A.

2012-01-01

Quantitative measurement of the levels of mRNA expression using real-time reverse transcription polymerase chain reaction (RT-PCR) has long been used for analyzing expression differences in tissue or cell lines of interest. This method has been used somewhat less frequently to measure the changes in gene expression due to perturbagens such as small molecules or siRNA. The availability of new instrumentation for liquid handling and real-time PCR analysis as well as the commercial availability of start-to-finish kits for RT-PCR has enabled the use of this method for high-throughput small-molecule screening on a scale comparable to traditional high-throughput screening (HTS) assays. This protocol focuses on the special considerations necessary for using quantitative RT-PCR as a primary small-molecule screening assay, including the different methods available for mRNA isolation and analysis. PMID:23487248

Selective inhibition of c-Myc/Max dimerization and DNA binding by small molecules.

PubMed

Kiessling, Anke; Sperl, Bianca; Hollis, Angela; Eick, Dirk; Berg, Thorsten

2006-07-01

bZip and bHLHZip protein family members comprise a large fraction of eukaryotic transcription factors and need to bind DNA in order to exert most of their fundamental biological roles. Their binding to DNA requires homo- or heterodimerization via alpha-helical domains, which generally do not contain obvious binding sites for small molecules. We have identified two small molecules, dubbed Mycro1 and Mycro2, which inhibit the protein-protein interactions between the bHLHZip proteins c-Myc and Max. Mycros are the first inhibitors of c-Myc/Max dimerization, which have been demonstrated to inhibit DNA binding of c-Myc with preference over other dimeric transcription factors in vitro. Mycros inhibit c-Myc-dependent proliferation, gene transcription, and oncogenic transformation in the low micromolar concentration range. Our data support the idea that dimeric transcription factors can be druggable even in the absence of obvious small-molecule binding pockets.

Small-molecule pheromones and hormones controlling nematode development.

PubMed

Butcher, Rebecca A

2017-05-17

The existence of small-molecule signals that influence development in Caenorhabditis elegans has been known for several decades, but only in recent years have the chemical structures of several of these signals been established. The identification of these signals has enabled connections to be made between these small molecules and fundamental signaling pathways in C. elegans that influence not only development but also metabolism, fertility, and lifespan. Spurred by these important discoveries and aided by recent advances in comparative metabolomics and NMR spectroscopy, the field of nematode chemistry has the potential to expand dramatically in the coming years. This Perspective will focus on small-molecule pheromones and hormones that influence developmental events in the nematode life cycle (ascarosides, dafachronic acids, and nemamides), will cover more recent work regarding the biosynthesis of these signals, and will explore how the discovery of these signals is transforming our understanding of nematode development and physiology.

A small molecule chemical chaperone optimizes its unfolded state contraction and denaturant like properties

NASA Astrophysics Data System (ADS)

Sharma, Sunny; Sarkar, Suparna; Paul, Simanta Sarani; Roy, Syamal; Chattopadhyay, Krishnananda

2013-12-01

Protein aggregation is believed to occur through the formation of misfolded conformations. It is expected that, in order to minimize aggregation, an effective small molecule chaperone would destabilize these intermediates. To study the mechanism of a chemical chaperone, we have designed a series of mutant proteins in which a tryptophan residue experiences different local environments and solvent exposures. We show that these mutants correspond to a series of conformationally altered proteins with varying degree of misfolding stress and aggregation propensities. Using arginine as a model small molecule, we show that a combination of unfolded state contraction and denaturant like properties results in selective targeting and destabilization of the partially folded proteins. In comparison, the effect of arginine towards the folded like control mutant, which is not aggregation prone, is significantly less. Other small molecules, lacking either of the above two properties, do not offer any specificity towards the misfolded proteins.

Side-chain Engineering of Benzo[1,2-b:4,5-b’]dithiophene Core-structured Small Molecules for High-Performance Organic Solar Cells

PubMed Central

Yin, Xinxing; An, Qiaoshi; Yu, Jiangsheng; Guo, Fengning; Geng, Yongliang; Bian, Linyi; Xu, Zhongsheng; Zhou, Baojing; Xie, Linghai; Zhang, Fujun; Tang, Weihua

2016-01-01

Three novel small molecules have been developed by side-chain engineering on benzo[1,2-b:4,5-b’]dithiophene (BDT) core. The typical acceptor-donor-acceptor (A-D-A) structure is adopted with 4,8-functionalized BDT moieties as core, dioctylterthiophene as π bridge and 3-ethylrhodanine as electron-withdrawing end group. Side-chain engineering on BDT core exhibits small but measurable effect on the optoelectronic properties of small molecules. Theoretical simulation and X-ray diffraction study reveal the subtle tuning of interchain distance between conjugated backbones has large effect on the charge transport and thus the photovoltaic performance of these molecules. Bulk-heterojunction solar cells fabricated with a configuration of ITO/PEDOT:PSS/SM:PC71BM/PFN/Al exhibit a highest power conversion efficiency (PCE) of 6.99% after solvent vapor annealing. PMID:27140224

Side-chain Engineering of Benzo[1,2-b:4,5-b']dithiophene Core-structured Small Molecules for High-Performance Organic Solar Cells.

PubMed

Yin, Xinxing; An, Qiaoshi; Yu, Jiangsheng; Guo, Fengning; Geng, Yongliang; Bian, Linyi; Xu, Zhongsheng; Zhou, Baojing; Xie, Linghai; Zhang, Fujun; Tang, Weihua

2016-05-03

Three novel small molecules have been developed by side-chain engineering on benzo[1,2-b:4,5-b']dithiophene (BDT) core. The typical acceptor-donor-acceptor (A-D-A) structure is adopted with 4,8-functionalized BDT moieties as core, dioctylterthiophene as π bridge and 3-ethylrhodanine as electron-withdrawing end group. Side-chain engineering on BDT core exhibits small but measurable effect on the optoelectronic properties of small molecules. Theoretical simulation and X-ray diffraction study reveal the subtle tuning of interchain distance between conjugated backbones has large effect on the charge transport and thus the photovoltaic performance of these molecules. Bulk-heterojunction solar cells fabricated with a configuration of ITO/PEDOT:PSS/SM:PC71BM/PFN/Al exhibit a highest power conversion efficiency (PCE) of 6.99% after solvent vapor annealing.

Small molecule solution-processed bulk heterojunction solar cells with inverted structure using porphyrin donor

NASA Astrophysics Data System (ADS)

Yamamoto, Takaki; Hatano, Junichi; Nakagawa, Takafumi; Yamaguchi, Shigeru; Matsuo, Yutaka

2013-01-01

Utilizing tetraethynyl porphyrin derivative (TE-Por) as a small molecule donor material, we fabricated a small molecule solution-processed bulk heterojunction (BHJ) solar cell with inverted structure, which exhibited 1.6% power conversion efficiency (JSC (short-circuit current) = 4.6 mA/cm2, VOC (open-circuit voltage) = 0.90 V, and FF (fill factor) = 0.39) in the device configuration indium tin oxide/TiOx (titanium sub-oxide)/[6,6]-phenyl-C61-butyric acid methyl ester:TE-Por (5:1)/MoOx (molybdenum sub-oxide)/Au under AM1.5 G illumination at 100 mW/cm2. Without encapsulation, the small molecule solution-processed inverted BHJ solar cell also showed remarkable durability to air, where it kept over 73% of its initial power conversion efficiency after storage for 28 days under ambient atmosphere in the dark.

Multivalent small molecule pan-RAS inhibitors

PubMed Central

Welsch, Matthew E.; Kaplan, Anna; Chambers, Jennifer M.; Stokes, Michael E.; Bos, Pieter H.; Zask, Arie; Zhang, Yan; Sanchez-Martin, Marta; Badgley, Michael A.; Huang, Christine S.; Tran, Timothy H.; Akkiraju, Hemanth; Brown, Lewis M.; Nandakumar, Renu; Cremers, Serge; Yang, Wan S.; Tong, Liang; Olive, Kenneth P.; Ferrando, Adolfo; Stockwell, Brent R.

2017-01-01

SUMMARY Design of small molecules that disrupt protein-protein interactions, including the interaction of RAS proteins and their effectors, have potential use as chemical probes and therapeutic agents. We describe here the synthesis and testing of potential small molecule pan-RAS ligands, which were designed to interact with adjacent sites on the surface of oncogenic KRAS. One compound, termed 3144, was found to bind to RAS proteins using microscale thermophoresis, nuclear magnetic resonance spectroscopy and isothermal titration calorimetry, and to exhibit lethality in cells partially dependent on expression of RAS proteins. This compound was metabolically stable in liver microsomes and displayed anti-tumor activity in xenograft mouse cancer models. These findings suggest that pan-RAS inhibition may be an effective therapeutic strategy for some cancers, and that structure-based design of small molecules targeting multiple adjacent sites to create multivalent inhibitors may be effective for some proteins. PMID:28235199

Speciation and preservation of CrVI and CrIII in finished drinking water matrices using collision cell ion chromatography-inductively coupled plasma-mass spectrometry

EPA Science Inventory

The polyatomic background at the major isotope of Cr was evaluated as a function of collision cell gas flow rate using three different mobile phases. The stability of CrVI was evaluated as a function of solution pH using an enriched 53CrVI. The recovery was ≥ 95% at pH 7.8 but...

Features of nanostructures sputtering

NASA Astrophysics Data System (ADS)

Kapustin, S. N.; Matveev, V. I.; Eseev, M. K.

2017-09-01

The research of ion sputtering of nanoparticles is interesting both from the fundamental point of view - for researching the interior structure of nanoobjects, and the economical one - nanostructures often play the role of functional supplements in composite materials under the radiation pressure. This process should be taken into account while creating objects decorated by nanoclusters during ion implantation. Polyatomic clusters obtained as a result of ion bombing could be used as nanodisperse catalysts or quantum points.

Complex small-molecule architectures regulate phenotypic plasticity in a nematode.

PubMed

Bose, Neelanjan; Ogawa, Akira; von Reuss, Stephan H; Yim, Joshua J; Ragsdale, Erik J; Sommer, Ralf J; Schroeder, Frank C

2012-12-07

Chemistry the worm's way: The nematode Pristionchus pacificus constructs elaborate small molecules from modified building blocks of primary metabolism, including an unusual xylopyranose-based nucleoside (see scheme). These compounds act as signaling molecules to control adult phenotypic plasticity and dauer development and provide examples of modular generation of structural diversity in metazoans. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Inhibiting prolyl isomerase activity by hybrid organic-inorganic molecules containing rhodium(II) fragments.

PubMed

Coughlin, Jane M; Kundu, Rituparna; Cooper, Julian C; Ball, Zachary T

2014-11-15

A small molecule containing a rhodium(II) tetracarboxylate fragment is shown to be a potent inhibitor of the prolyl isomerase FKBP12. The use of small molecules conjugates of rhodium(II) is presented as a general strategy for developing new protein inhibitors based on distinct structural and sequence features of the enzyme active site. Copyright © 2014 Elsevier Ltd. All rights reserved.

Affinity modulation of small-molecule ligands by borrowing endogenous protein surfaces

PubMed Central

Briesewitz, Roger; Ray, Gregory T.; Wandless, Thomas J.; Crabtree, Gerald R.

1999-01-01

A general strategy is described for improving the binding properties of small-molecule ligands to protein targets. A bifunctional molecule is created by chemically linking a ligand of interest to another small molecule that binds tightly to a second protein. When the ligand of interest is presented to the target protein by the second protein, additional protein–protein interactions outside of the ligand-binding sites serve either to increase or decrease the affinity of the binding event. We have applied this approach to an intractable target, the SH2 domain, and demonstrate a 3-fold enhancement over the natural peptide. This approach provides a way to modulate the potency and specificity of biologically active compounds. PMID:10051576

Large-Scale Validation of Mixed-Solvent Simulations to Assess Hotspots at Protein-Protein Interaction Interfaces.

PubMed

Ghanakota, Phani; van Vlijmen, Herman; Sherman, Woody; Beuming, Thijs

2018-04-23

The ability to target protein-protein interactions (PPIs) with small molecule inhibitors offers great promise in expanding the druggable target space and addressing a broad range of untreated diseases. However, due to their nature and function of interacting with protein partners, PPI interfaces tend to extend over large surfaces without the typical pockets of enzymes and receptors. These features present unique challenges for small molecule inhibitor design. As such, determining whether a particular PPI of interest could be pursued with a small molecule discovery strategy requires an understanding of the characteristics of the PPI interface and whether it has hotspots that can be leveraged by small molecules to achieve desired potency. Here, we assess the ability of mixed-solvent molecular dynamic (MSMD) simulations to detect hotspots at PPI interfaces. MSMD simulations using three cosolvents (acetonitrile, isopropanol, and pyrimidine) were performed on a large test set of 21 PPI targets that have been experimentally validated by small molecule inhibitors. We compare MSMD, which includes explicit solvent and full protein flexibility, to a simpler approach that does not include dynamics or explicit solvent (SiteMap) and find that MSMD simulations reveal additional information about the characteristics of these targets and the ability for small molecules to inhibit the PPI interface. In the few cases were MSMD simulations did not detect hotspots, we explore the shortcomings of this technique and propose future improvements. Finally, using Interleukin-2 as an example, we highlight the advantage of the MSMD approach for detecting transient cryptic druggable pockets that exists at PPI interfaces.

Inhibitor of PI3K/Akt Signaling Pathway Small Molecule Promotes Motor Neuron Differentiation of Human Endometrial Stem Cells Cultured on Electrospun Biocomposite Polycaprolactone/Collagen Scaffolds.

PubMed

Ebrahimi-Barough, Somayeh; Hoveizi, Elham; Yazdankhah, Meysam; Ai, Jafar; Khakbiz, Mehrdad; Faghihi, Faezeh; Tajerian, Roksana; Bayat, Neda

2017-05-01

Small molecules as useful chemical tools can affect cell differentiation and even change cell fate. It is demonstrated that LY294002, a small molecule inhibitor of phosphatidylinositol 3-kinase (PI3K)/Akt signal pathway, can inhibit proliferation and promote neuronal differentiation of mesenchymal stem cells (MSCs). The purpose of this study was to investigate the differentiation effect of Ly294002 small molecule on the human endometrial stem cells (hEnSCs) into motor neuron-like cells on polycaprolactone (PCL)/collagen scaffolds. hEnSCs were cultured in a neurogenic inductive medium containing 1 μM LY294002 on the surface of PCL/collagen electrospun fibrous scaffolds. Cell attachment and viability of cells on scaffolds were characterized by scanning electron microscope (SEM) and 3-(4,5-dimethylthiazoyl-2-yl)2,5-diphenyltetrazolium bromide (MTT) assay. The expression of neuron-specific markers was assayed by real-time PCR and immunocytochemistry analysis after 15 days post induction. Results showed that attachment and differentiation of hEnSCs into motor neuron-like cells on the scaffolds with Ly294002 small molecule were higher than that of the cells on tissue culture plates as control group. In conclusion, PCL/collagen electrospun scaffolds with Ly294002 have potential for being used in neural tissue engineering because of its bioactive and three-dimensional structure which enhances viability and differentiation of hEnSCs into neurons through inhibition of the PI3K/Akt pathway. Thus, manipulation of this pathway by small molecules can enhance neural differentiation.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Iconaru, Luigi I.; Ban, David; Bharatham, Kavitha

In disordered proteins we see that they are highly prevalent in biological systems. They control myriad signaling and regulatory processes, and their levels and/or cellular localization are often altered in human disease. In contrast to folded proteins, disordered proteins, due to conformational heterogeneity and dynamics, are not considered viable drug targets. We challenged this paradigm by identifying through NMR-based screening small molecules that bound specifically, albeit weakly, to the disordered cell cycle regulator, p27 Kip1 (p27). Moreover, two groups of molecules bound to sites created by transient clusters of aromatic residues within p27. Conserved chemical features within these two groupsmore » of small molecules exhibited complementarity to their binding sites within p27, establishing structure-activity relationships for small molecule: disordered protein interactions. Finally, one compound counteracted the Cdk2/cyclin A inhibitory function of p27 in vitro, providing proof-of- principle that small molecules can inhibit the function of a disordered protein (p27) through sequestration in a conformation incapable of folding and binding to a natural regulatory target (Cdk2/cyclin A).« less

Tulane/Xavier Vaccine Development/Engineering Project

DTIC Science & Technology

2009-02-01

spectroscopic studies with polar dyes (e.g. proflavine ) have verified these compounds’ ability to encapsulate and solvate small polar dye molecules in...systems. Fluorescent microscopy studies verify that they significantly enhance the transport of polar small molecules ( proflavin dye) through

Exploring Molecular Complexity of the Diffuse and Translucent Gas and PhotoDissociation Regions

NASA Astrophysics Data System (ADS)

McCarthy, Michael

This proposal requests funds to continue a laboratory program in close coordination with radio astronomical observations dedicated to the study of highly reactive polyatomic molecular ions in low density regions and photo-dissociation regions (PDRs). In doing so, the proposed studies will advance our understanding of the chemistry beyond light ions that have been observed so successfully in these regions with Herschel and recently extended with SOFIA, and thereby critically address a significant but unresolved question in molecular astronomy: Are larger molecules formed in a bottom-up or top-down chemistry? The rotational spectra of most new molecular ions will be detected in the laboratory in a resonant microwave cavity, followed either by microwave/millimeterwave double resonance or millimeter/THz absorption to better characterize their spectrum in bands covered by the heterodyne receivers HIFI on Herschel and GREAT on SOFIA. In collaboration with radioastronomer colleagues, we will search for the new ions in the published survey of the PDR region of the Orion Bar and archival data of other PDRs observed with the IRAM 30 m telescope; retrieve and analyze archival data from Herschel; and undertake searches for some of the new ions in PDRs and low density regions with SOFIA. This work will also have a strong bearing on proposed Early Release Science (ERS) observations of dense PDRs with the James Webb Space Telescope (JWST). The laboratory effort will build on previous work on molecular ions , specifically detection of the rotational spectra of a number of positive ions of astronomical interest such as H2NCO+, CCCH+, the cis- and trans isomers of HOSO+, HNCOH+, and H2CC(H)CNH+. We will focus our efforts on positive ions derived from closed-shell neutral molecules, radicals, and carbenes whose rotational spectra have been observed in our laboratory, and nearly all of which have also been identified in galactic molecular clouds. Examples of the ions we seek include polyatomic ions such as CN+, HCCCN+, HNCO+, c-C3H2+, etc. Collaborations with leading theoretical groups to accurately predict spectroscopic constants of the new ions will enhance the proposed laboratory investigations. Instrumental refinement will also be undertaken with particular emphasis on construction of a new cryogenically cooled ( 6 K) buffer gas cell. This ultra-sensitive instrument will possess a system temperature that is nearly 50 times lower than our most sensitive cavity spectrometer, and one close to the fundamental limit set by modern technology, thereby greatly enhancing our ability to detect elusive molecular ions that are produced in very low steady state concentrations. The essential capabilities of this instrument have already been demonstrated in collaborative investigations. Our laboratory program is well aligned with NASA's overall mission, because we seek to understand the role of the chemical bond on a cosmic scale and to provide a firm chemical foundation by which more complicated questions of biological origins can be addressed. The work here also provides much basic information to aid subsequent astronomical searches, particularly in the infrared. Finally, our research program is an excellent vehicle for integrating research and education. It provides exposure to quite diverse areas of science in a setting which encourages student initiative and independent investigation.

Mass action at the single-molecule level.

PubMed

Shon, Min Ju; Cohen, Adam E

2012-09-05

We developed a system to reversibly encapsulate small numbers of molecules in an array of nanofabricated "dimples". This system enables highly parallel, long-term, and attachment-free studies of molecular dynamics via single-molecule fluorescence. In studies of bimolecular reactions of small numbers of confined molecules, we see phenomena that, while expected from basic statistical mechanics, are not observed in bulk chemistry. Statistical fluctuations in the occupancy of sealed reaction chambers lead to steady-state fluctuations in reaction equilibria and rates. These phenomena are likely to be important whenever reactions happen in confined geometries.

Persistence length of collagen molecules based on nonlocal viscoelastic model.

PubMed

Ghavanloo, Esmaeal

2017-12-01

Persistence length is one of the most interesting properties of a molecular chain, which is used to describe the stiffness of a molecule. The experimentally measured values of the persistence length of the collagen molecule are widely scattered from 14 to 180 nm. Therefore, an alternative approach is highly desirable to predict the persistence length of a molecule and also to explain the experimental results. In this paper, a nonlocal viscoelastic model is developed to obtain the persistence length of the collagen molecules in solvent. A new explicit formula is proposed for the persistence length of the molecule with the consideration of the small-scale effect, viscoelastic properties of the molecule, loading frequency, and viscosity of the solvent. The presented model indicates that there exists a range of molecule lengths in which the persistence length strongly depends on the frequency and spatial mode of applied loads, small-scale effect, and viscoelastic properties of the collagen.

Caenorhabditis elegans chemical biology: lessons from small molecules

USDA-ARS?s Scientific Manuscript database

How can we complement Caenorhabditis elegans genomics and proteomics with a comprehensive structural and functional annotation of its metabolome? Several lines of evidence indicate that small molecules of largely undetermined structure play important roles in C. elegans biology, including key pathw...

Solution-processed small molecule:fullerene bulk-heterojunction solar cells: impedance spectroscopy deduced bulk and interfacial limits to fill-factors.

PubMed

Guerrero, Antonio; Loser, Stephen; Garcia-Belmonte, Germà; Bruns, Carson J; Smith, Jeremy; Miyauchi, Hiroyuki; Stupp, Samuel I; Bisquert, Juan; Marks, Tobin J

2013-10-21

Using impedance spectroscopy, we demonstrate that the low fill factor (FF) typically observed in small molecule solar cells is due to hindered carrier transport through the active layer and hindered charge transfer through the anode interfacial layer (IFL). By carefully tuning the active layer thickness and anode IFL in BDT(TDPP)2 solar cells, the FF is increased from 33 to 55% and the PCE from 1.9 to 3.8%. These results underscore the importance of simultaneously optimizing active layer thickness and IFL in small molecule solar cells.

Inhibitors of voltage-gated sodium channel Nav1.7: patent applications since 2010.

PubMed

Sun, Shaoyi; Cohen, Charles J; Dehnhardt, Christoph M

2014-09-01

There has been intense interest in developing inhibitors of the sodium channel Nav1.7 because genetic studies have established very strong validation for the efficacy to alleviate both inflammatory and neuropathic pain. This review summarizes patent applications targeting Nav1.7 since 2010 until May, 2014. We have classified the patents into three categories as follows: small molecules with well-defined molecular selectivity among sodium channel isoforms; biologicals with well-defined molecular selectivity; and, small molecules that inhibit Nav1.7 with unknown molecular selectivity. Most of the review is dedicated to small molecule selective compounds.

Photobleaching dynamics in small molecule vs.  polymer organic photovoltaic blends with 1,7-bis-trifluoromethylfullerene

DOE PAGES

Garner, Logan E.; Nellissery Viswanathan, Vinila; Arias, Dylan H.; ...

2018-02-27

Two organic photovoltaic (OPV) donor materials (one polymer and one small molecule) are synthesized from the same constituent building blocks, namely thiophene units, cyclopentathiophene dione (CTD), and cyclopentadithiophene (CPDT). Photobleaching dynamics of these donor materials are then studied under white light illumination in air with blends of PC 70BM and the bistrifluoromethylfullerene 1,7-C 60(CF 3) 2. For both the polymer and small molecule blends, C 60(CF 3) 2 stabilizes the initial rate of photobleaching by a factor of 15 relative to PC70BM. However, once the small molecule:C 60(CF 3) 2 blend bleaches to ~80% of its initial optical density, themore » rate of photobleaching dramatically accelerates, which is not observed in the analagous polymer blend. We probe that phenomenon using time-resovled photoluminescence (TRPL) to measure PL quenching efficiencies at defined intervals during the photobleaching experiments. The data indicates the small molecule donor and C 60(CF 3) 2 acceptor significantly de-mix with time, after which the blend begins to bleach at approximately the same rate as the neat donor sample. The work suggests that perfluoroalkylfullerenes have great potential to stabilize certain OPV active layers toward photodegradation, provided their morphology is stable.« less

Photobleaching dynamics in small molecule vs.  polymer organic photovoltaic blends with 1,7-bis-trifluoromethylfullerene

DOE Office of Scientific and Technical Information (OSTI.GOV)

Garner, Logan E.; Nellissery Viswanathan, Vinila; Arias, Dylan H.

Two organic photovoltaic (OPV) donor materials (one polymer and one small molecule) are synthesized from the same constituent building blocks, namely thiophene units, cyclopentathiophene dione (CTD), and cyclopentadithiophene (CPDT). Photobleaching dynamics of these donor materials are then studied under white light illumination in air with blends of PC 70BM and the bistrifluoromethylfullerene 1,7-C 60(CF 3) 2. For both the polymer and small molecule blends, C 60(CF 3) 2 stabilizes the initial rate of photobleaching by a factor of 15 relative to PC70BM. However, once the small molecule:C 60(CF 3) 2 blend bleaches to ~80% of its initial optical density, themore » rate of photobleaching dramatically accelerates, which is not observed in the analagous polymer blend. We probe that phenomenon using time-resovled photoluminescence (TRPL) to measure PL quenching efficiencies at defined intervals during the photobleaching experiments. The data indicates the small molecule donor and C 60(CF 3) 2 acceptor significantly de-mix with time, after which the blend begins to bleach at approximately the same rate as the neat donor sample. The work suggests that perfluoroalkylfullerenes have great potential to stabilize certain OPV active layers toward photodegradation, provided their morphology is stable.« less

A Potent and Selective Quinoxalinone-Based STK33 Inhibitor Does Not Show Synthetic Lethality in KRAS-Dependent Cells

PubMed Central

2012-01-01

The KRAS oncogene is found in up to 30% of all human tumors. In 2009, RNAi experiments revealed that lowering mRNA levels of a transcript encoding the serine/threonine kinase STK33 was selectively toxic to KRAS-dependent cancer cell lines, suggesting that small-molecule inhibitors of STK33 might selectively target KRAS-dependent cancers. To test this hypothesis, we initiated a high-throughput screen using compounds in the Molecular Libraries Small Molecule Repository (MLSMR). Several hits were identified, and one of these, a quinoxalinone derivative, was optimized. Extensive SAR studies were performed and led to the chemical probe ML281 that showed low nanomolar inhibition of purified recombinant STK33 and a distinct selectivity profile as compared to other STK33 inhibitors that were reported in the course of these studies. Even at the highest concentration tested (10 μM), ML281 had no effect on the viability of KRAS-dependent cancer cells. These results are consistent with other recent reports using small-molecule STK33 inhibitors. Small molecules having different chemical structures and kinase-selectivity profiles are needed to fully understand the role of STK33 in KRAS-dependent cancers. In this regard, ML281 is a valuable addition to small-molecule probes of STK33. PMID:23256033

DBDA as a Novel Matrix for the Analyses of Small Molecules and Quantification of Fatty Acids by Negative Ion MALDI-TOF MS

NASA Astrophysics Data System (ADS)

Ling, Ling; Li, Ying; Wang, Sheng; Guo, Liming; Xiao, Chunsheng; Chen, Xuesi; Guo, Xinhua

2018-01-01

Matrix interference ions in low mass range has always been a concern when using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) to analyze small molecules (<500 Da). In this work, a novel matrix, N1,N4-dibenzylidenebenzene-1,4-diamine (DBDA) was synthesized for the analyses of small molecules by negative ion MALDI-TOF MS. Notably, only neat ions ([M-H]-) of fatty acids without matrix interference appeared in the mass spectra and the limit of detection (LOD) reached 0.3 fmol. DBDA also has great performance towards other small molecules such as amino acids, peptides, and nucleotide. Furthermore, with this novel matrix, the free fatty acids in serum were quantitatively analyzed based on the correlation curves with correlation coefficient of 0.99. In addition, UV-Vis experiments and molecular orbital calculations were performed to explore mechanism about DBDA used as matrix in the negative ion mode. The present work shows that the DBDA matrix is a highly sensitive matrix with few interference ions for analysis of small molecules. Meanwhile, DBDA is able to precisely quantify the fatty acids in real biological samples. [Figure not available: see fulltext.

Simulation-based cheminformatic analysis of organelle-targeted molecules: lysosomotropic monobasic amines

PubMed Central

Zhang, Xinyuan; Zheng, Nan

2008-01-01

Cell-based molecular transport simulations are being developed to facilitate exploratory cheminformatic analysis of virtual libraries of small drug-like molecules. For this purpose, mathematical models of single cells are built from equations capturing the transport of small molecules across membranes. In turn, physicochemical properties of small molecules can be used as input to simulate intracellular drug distribution, through time. Here, with mathematical equations and biological parameters adjusted so as to mimic a leukocyte in the blood, simulations were performed to analyze steady state, relative accumulation of small molecules in lysosomes, mitochondria, and cytosol of this target cell, in the presence of a homogenous extracellular drug concentration. Similarly, with equations and parameters set to mimic an intestinal epithelial cell, simulations were also performed to analyze steady state, relative distribution and transcellular permeability in this non-target cell, in the presence of an apical-to-basolateral concentration gradient. With a test set of ninety-nine monobasic amines gathered from the scientific literature, simulation results helped analyze relationships between the chemical diversity of these molecules and their intracellular distributions. Electronic supplementary material The online version of this article (doi:10.1007/s10822-008-9194-7) contains supplementary material, which is available to authorized users. PMID:18338229

Signal-enhancer molecules encapsulated liposome as a valuable sensing and amplification platform combining the aptasensor for ultrasensitive ECL immunoassay.

PubMed

Mao, Li; Yuan, Ruo; Chai, Yaqin; Zhuo, Ying; Xiang, Yun

2011-06-15

An innovatory ECL immunoassay strategy was proposed to detect the newly developing heart failure biomarker N-terminal pro-brain natriuretic peptide (NT-proBNP). Firstly, this strategy used small molecules encapsulated liposome as immune label to construct a sandwich immune sensing platform for NT-proBNP. Then the ECL aptasensor was prepared to collect and detect the small molecules released from the liposome. Finally, based on the ECL signal changes caused by the small molecules, the ECL signal indirectly reflected the level of NT-proBNP antigen. In this experiment, the cocaine was chosen as the proper small molecule that can act as signal-enhancer to enhance the ECL of Ru(bpy)(3)(2+). The cocaine-encapsulated liposomes were successfully characterized by TEM. The quantificational calculation proved the ∼5.3×10(3) cocaine molecules per liposome enough to perform the assignment of signal amplification. The cocaine-binding ECL aptasensor further promoted the work aimed at amplifying signal. The performance of NT-proBNP assay by the proposed strategy exhibited high sensitivity and high specificities with a linear relationship over 0.01-500 ng mL(-1) range, and a detection limit down to 0.77 pg mL(-1). Copyright © 2011 Elsevier B.V. All rights reserved.

Desorption Induced by KEV Molecular and Cluster Projectiles.

NASA Astrophysics Data System (ADS)

Blain, Matthew Glenn

1990-01-01

A new experimental method has been developed for studying negative secondary ion (SI) emission from solid surfaces bombarded by polyatomic primary ions of 5 to 30 keV. The method is based on the time-of-flight (TOF) analysis of primary ions which are produced by either ^ {252}Cf fission fragment induced desorption or by extraction from a liquid metal ion source, and then accelerated into a field free region. The primary ions included organic monomer, dimer, and fragment ions of coronene and phenylalanine, (CsI)_ nCs ^{+} cluster ions, and Au _sp{n}{+} cluster ions. Secondary electrons, emitted from a target surface upon primary ion impact, are used to identify which primary ion has hit the surface. An event-by-event coincidence counting technique allows several secondary ion TOF spectra, correlated to several different primary ions, to be acquired simultaneously. Negative SI yields from organic (phenylalanine and dinitrostilbene), CsI, and Au surfaces have been measured for a number of different mono- and polyatomic primary ions. The results show, for example, yields ranging from 1 to 10% for phenylalanine (M-H) ^{ -}, 1 to 10% for I^{-} , and 1 to 5% for Au^{-} , with Cs_2I^ {+} and Cs_3I _sp{2}{+} clusters as projectiles. Yields for the same surfaces using Cs ^{+} primary ions are much less than 1%, indicating that SI yields are enhanced with clusters. A yield enhancement occurs when the SI yield per atom of a polyatomic projectile is greater than the SI yield of its monoatomic equivalent, at the same velocity. Thus, a (M-H) ^{-} yield increase of a factor of 50, when phenylalanine is bombarded with Cs_3I_sp{2} {+} instead of Cs^{+ }, represents a yield enhancement factor of 10. For the projectiles and samples studied, it was observed that the heavier the mass of the constituents of a projectile, the larger the enhancement effects, and that the largest yield enhancements (with CsI and Au _ n projectiles) occur for the organic target, phenylalanine. One possible explanation for the larger enhancements with organics, namely a thermal spike process, appears unlikely. Experiments with high and low melting point isomers of dinitrostilbene, bombarded with Cs _2I^{+} and Cs^{+} projectiles, showed larger Cs_2I^ {+} yield enhancements for the high melting point isomer.

A density functional theory based approach for predicting melting points of ionic liquids

DOE PAGES

Chen, Lihua; Bryantsev, Vyacheslav S.

2017-01-17

Accurate prediction of melting points of ILs is important both from the fundamental point of view and from the practical perspective for screening ILs with low melting points and broadening their utilization in a wider temperature range. In this work, we present an ab initio approach to calculating melting points of ILs with known crystal structures and illustrate its application for a series of 11 ILs containing imidazolium/pyrrolidinium cations and halide/polyatomic fluoro-containing anions. The melting point is determined as a temperature at which the Gibbs free energy of fusion is zero. The Gibbs free energy of fusion can be expressedmore » through the use of the Born-Fajans-Haber cycle via the lattice free energy of forming a solid IL from gaseous phase ions and the sum of the solvation free energies of ions comprising IL. Dispersion-corrected density functional theory (DFT) involving (semi)local (PBE-D3) and hybrid exchange-correlation (HSE06-D3) functionals is applied to estimate the lattice enthalpy, entropy, and free energy. The ions solvation free energies are calculated with the SMD-generic-IL solvation model at the M06-2X/6-31+G(d) level of theory under standard conditions. The melting points of ILs computed with the HSE06-D3 functional are in good agreement with the experimental data, with a mean absolute error of 30.5 K and a mean relative error of 8.5%. The model is capable of accurately reproducing the trends in melting points upon variation of alkyl substituents in organic cations and replacement one anion by another. The results verify that the lattice energies of ILs containing polyatomic fluoro-containing anions can be approximated reasonably well using the volume-based thermodynamic approach. However, there is no correlation of the computed lattice energies with molecular volume for ILs containing halide anions. Moreover, entropies of solid ILs follow two different linear relationships with molecular volume for halides and polyatomic fluoro-containing anions. As a result, continuous progress in predicting crystal structures of organic salts with halide anions will be a key factor for successful prediction of melting points with no prior knowledge of the crystal structure.« less

Silicon isotope ratio measurements by inductively coupled plasma tandem mass spectrometry for alteration studies of nuclear waste glasses.

PubMed

Gourgiotis, Alkiviadis; Ducasse, Thomas; Barker, Evelyne; Jollivet, Patrick; Gin, Stéphane; Bassot, Sylvain; Cazala, Charlotte

2017-02-15

High-level, long-lived nuclear waste arising from spent fuel reprocessing is vitrified in silicate glasses for final disposal in deep geologic formations. In order to better understand the mechanisms driving glass dissolution, glass alteration studies, based on silicon isotope ratio monitoring of 29 Si-doped aqueous solutions, were carried out in laboratories. This work explores the capabilities of the new type of quadrupole-based ICP-MS, the Agilent 8800 tandem quadrupole ICP-MS/MS, for accurate silicon isotope ratio determination for alteration studies of nuclear waste glasses. In order to avoid silicon polyatomic interferences, a new analytical method was developed using O 2 as the reaction gas in the Octopole Reaction System (ORS), and silicon isotopes were measured in mass-shift mode. A careful analysis of the potential polyatomic interferences on SiO + and SiO 2 + ion species was performed, and we found that SiO + ion species suffer from important polyatomic interferences coming from the matrix of sample and standard solutions (0.5M HNO 3 ). For SiO 2 + , no interferences were detected, and thus, these ion species were chosen for silicon isotope ratio determination. A number of key settings for accurate isotope ratio analysis like, detector dead time, integration time, number of sweeps, wait time offset, memory blank and instrumental mass fractionation, were considered and optimized. Particular attention was paid to the optimization of abundance sensitivity of the quadrupole mass filter before the ORS. We showed that poor abundance sensitivity leads to a significant shift of the data away from the Exponential Mass Fractionation Law (EMFL) due to the spectral overlaps of silicon isotopes combined with different oxygen isotopes (i.e. 28 Si 16 O 18 O + , 30 Si 16 O 16 O + ). The developed method was validated by measuring a series of reference solutions with different 29 Si enrichment. Isotope ratio trueness, uncertainty and repeatability were found to be <0.2%, <0.5% and <0.6%, respectively. These performances meet the requirements of the studies of nuclear glasses alteration and open up possibilities to use this method for precise determination of silicon content in natural samples by Isotope Dilution. Copyright © 2016 Elsevier B.V. All rights reserved.

A density functional theory based approach for predicting melting points of ionic liquids

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Lihua; Bryantsev, Vyacheslav S.

Accurate prediction of melting points of ILs is important both from the fundamental point of view and from the practical perspective for screening ILs with low melting points and broadening their utilization in a wider temperature range. In this work, we present an ab initio approach to calculating melting points of ILs with known crystal structures and illustrate its application for a series of 11 ILs containing imidazolium/pyrrolidinium cations and halide/polyatomic fluoro-containing anions. The melting point is determined as a temperature at which the Gibbs free energy of fusion is zero. The Gibbs free energy of fusion can be expressedmore » through the use of the Born-Fajans-Haber cycle via the lattice free energy of forming a solid IL from gaseous phase ions and the sum of the solvation free energies of ions comprising IL. Dispersion-corrected density functional theory (DFT) involving (semi)local (PBE-D3) and hybrid exchange-correlation (HSE06-D3) functionals is applied to estimate the lattice enthalpy, entropy, and free energy. The ions solvation free energies are calculated with the SMD-generic-IL solvation model at the M06-2X/6-31+G(d) level of theory under standard conditions. The melting points of ILs computed with the HSE06-D3 functional are in good agreement with the experimental data, with a mean absolute error of 30.5 K and a mean relative error of 8.5%. The model is capable of accurately reproducing the trends in melting points upon variation of alkyl substituents in organic cations and replacement one anion by another. The results verify that the lattice energies of ILs containing polyatomic fluoro-containing anions can be approximated reasonably well using the volume-based thermodynamic approach. However, there is no correlation of the computed lattice energies with molecular volume for ILs containing halide anions. Moreover, entropies of solid ILs follow two different linear relationships with molecular volume for halides and polyatomic fluoro-containing anions. As a result, continuous progress in predicting crystal structures of organic salts with halide anions will be a key factor for successful prediction of melting points with no prior knowledge of the crystal structure.« less

Highly Accurate and Precise Infrared Transition Frequencies of the H_3^+ Cation

NASA Astrophysics Data System (ADS)

Perry, Adam J.; Markus, Charles R.; Hodges, James N.; Kocheril, G. Stephen; McCall, Benjamin J.

2016-06-01

Calculation of ab initio potential energy surfaces for molecules to high accuracy is only manageable for a handful of molecular systems. Among them is the simplest polyatomic molecule, the H_3^+ cation. In order to achieve a high degree of accuracy (<1 wn) corrections must be made to the to the traditional Born-Oppenheimer approximation that take into account not only adiabatic and non-adiabatic couplings, but quantum electrodynamic corrections as well. For the lowest rovibrational levels the agreement between theory and experiment is approaching 0.001 wn, whereas the agreement is on the order of 0.01 - 0.1 wn for higher levels which are closely rivaling the uncertainties on the experimental data. As method development for calculating these various corrections progresses it becomes necessary for the uncertainties on the experimental data to be improved in order to properly benchmark the calculations. Previously we have measured 20 rovibrational transitions of H_3^+ with MHz-level precision, all of which have arisen from low lying rotational levels. Here we present new measurements of rovibrational transitions arising from higher rotational and vibrational levels. These transitions not only allow for probing higher energies on the potential energy surface, but through the use of combination differences, will ultimately lead to prediction of the "forbidden" rotational transitions with MHz-level accuracy. L.G. Diniz, J.R. Mohallem, A. Alijah, M. Pavanello, L. Adamowicz, O.L. Polyansky, J. Tennyson Phys. Rev. A (2013), 88, 032506 O.L. Polyansky, A. Alijah, N.F. Zobov, I.I. Mizus, R.I. Ovsyannikov, J. Tennyson, L. Lodi, T. Szidarovszky, A.G. Császár Phil. Trans. R. Soc. A (2012), 370, 5014 J.N. Hodges, A.J. Perry, P.A. Jenkins II, B.M. Siller, B.J. McCall J. Chem. Phys. (2013), 139, 164201 A.J. Perry, J.N. Hodges, C.R. Markus, G.S. Kocheril, B.J. McCall J. Molec. Spectrosc. (2015), 317, 71-73.

Stochastic voyages into uncharted chemical space produce a representative library of all possible drug-like compounds

PubMed Central

Virshup, Aaron M.; Contreras-García, Julia; Wipf, Peter; Yang, Weitao; Beratan, David N.

2013-01-01

The “small molecule universe” (SMU), the set of all synthetically feasible organic molecules of 500 Daltons molecular weight or less, is estimated to contain over 1060 structures, making exhaustive searches for structures of interest impractical. Here, we describe the construction of a “representative universal library” spanning the SMU that samples the full extent of feasible small molecule chemistries. This library was generated using the newly developed Algorithm for Chemical Space Exploration with Stochastic Search (ACSESS). ACSESS makes two important contributions to chemical space exploration: it allows the systematic search of the unexplored regions of the small molecule universe, and it facilitates the mining of chemical libraries that do not yet exist, providing a near-infinite source of diverse novel compounds. PMID:23548177

Chembank | Office of Cancer Genomics

Cancer.gov

Funded in large part by the Initiative for Chemical Genetics (ICG), Chembank is an interactive database for small molecules. It contains data from hundreds of biomedically relevant small molecule screens that involved hundreds-of-thousands of compounds. Chembank also provides analysis tools to facilitate data mining.

Research in Electronics - JSEP.

DTIC Science & Technology

1981-03-01

17. H . Helvajian and C. Wittig, "Collisional Quenching of HgBr(B 2 4i/2), Opt. Commun. 30, 189 (1979). 18. H . Reisler and C. Wittig, "Electronic...Luminescence Resulting from IR Multiple Photon Excitation, " in ’Photoselective Chemistry, Part I,’ J. Jortner ed., Wiley, 1981. 19. H . Helvajian , M...to Intramolecular V E coupling in IR Laser Excited Polyatomics, " J. Chem. Phys., in press. 22. H . Helvajian and C. Wittig, "Vibrational Quenching of

In Situ Determination of Trace Elements in Fish Otoliths by Laser Ablation Double Focusing Sector Field Inductively Coupled Plasma Mass Spectrometry Using a Solution Standard Addition Calibration Method

NASA Astrophysics Data System (ADS)

Chen, Z.; Jones, C. M.

2002-05-01

Microchemistry of fish otoliths (fish ear bones) is a very useful tool for monitoring aquatic environments and fish migration. However, determination of the elemental composition in fish otolith by ICP-MS has been limited to either analysis of dissolved sample solution or measurement of limited number of trace elements by laser ablation (LA)- ICP-MS due to low sensitivity, lack of available calibration standards, and complexity of polyatomic molecular interference. In this study, a method was developed for in situ determination of trace elements in fish otoliths by laser ablation double focusing sector field ultra high sensitivity Finnigan Element 2 ICP-MS using a solution standard addition calibration method. Due to the lack of matrix-match solid calibration standards, sixteen trace elements (Na, Mg, P, Cr, Mn, Fe, Ni, Cu, Rb, Sr, Y, Cd, La, Ba, Pb and U) were determined using a solution standard calibration with Ca as an internal standard. Flexibility, easy preparation and stable signals are the advantages of using solution calibration standards. In order to resolve polyatomic molecular interferences, medium resolution (M/delta M > 4000) was used for some elements (Na, Mg, P, Cr, Mn, Fe, Ni, and Cu). Both external calibration and standard addition quantification strategies are compared and discussed. Precision, accuracy, and limits of detection are presented.

Radiative interactions in molecular gases under local and nonlocal thermodynamic equilibrium conditions

NASA Technical Reports Server (NTRS)

Tiwari, S. N.; Jha, M. K.

1993-01-01

Basic formulations, analyses, and numerical procedures are presented to investigate radiative heat interactions in diatomic and polyatomic gases under local and nonlocal thermodynamic equilibrium conditions. Essential governing equations are presented for both gray and nongray gases. Information is provided on absorption models, relaxation times, and transfer equations. Radiative flux equations are developed which are applicable under local and nonlocal thermodynamic equilibrium conditions. The problem is solved for fully developed laminar incompressible flows between two parallel plates under the boundary condition of a uniform surface heat flux. For specific applications, three diatomic and three polyatomic gases are considered. The results are obtained numerically by employing the method of variation of parameters. The results are compared under local and nonlocal thermodynamic equilibrium conditions at different temperature and pressure conditions. Both gray and nongray studies are conducted extensively for all molecular gases considered. The particular gases selected for this investigation are CO, NO, OH, CO2, H2O, and CH4. The temperature and pressure range considered are 300-2000 K and 0.1-10 atmosphere, respectively. In general, results demonstrate that the gray gas approximation overestimates the effect of radiative interaction for all conditions. The conditions of NLTE, however, result in underestimation of radiative interactions. The method developed for this study can be extended to solve complex problems of radiative heat transfer involving nonequilibrium phenomena.

Conformational analysis by intersection: CONAN.

PubMed

Smellie, Andrew; Stanton, Robert; Henne, Randy; Teig, Steve

2003-01-15

As high throughput techniques in chemical synthesis and screening improve, more demands are placed on computer assisted design and virtual screening. Many of these computational methods require one or more three-dimensional conformations for molecules, creating a demand for a conformational analysis tool that can rapidly and robustly cover the low-energy conformational spaces of small molecules. A new algorithm of intersection is presented here, which quickly generates (on average <0.5 seconds/stereoisomer) a complete description of the low energy conformational space of a small molecule. The molecule is first decomposed into nonoverlapping nodes N (usually rings) and overlapping paths P with conformations (N and P) generated in an offline process. In a second step the node and path data are combined to form distinct conformers of the molecule. Finally, heuristics are applied after intersection to generate a small representative collection of conformations that span the conformational space. In a study of approximately 97,000 randomly selected molecules from the MDDR, results are presented that explore these conformations and their ability to cover low-energy conformational space. Copyright 2002 Wiley Periodicals, Inc. J Comput Chem 24: 10-20, 2003

Chemical correction of pre-mRNA splicing defects associated with sequestration of muscleblind-like 1 protein by expanded r(CAG) transcripts

PubMed Central

Kumar, Amit; Parkesh, Raman; Sznajder, Lukasz J.; Childs-Disney, Jessica; Sobczak, Krzysztof; Disney, Matthew D.

2012-01-01

Recently, it was reported that expanded r(CAG) triplet repeats (r(CAG)exp) associated with untreatable neurological diseases cause pre-mRNA mis-splicing likely due to sequestration of muscleblind-like 1 (MBNL1) splicing factor. Bioactive small molecules that bind the 5’CAG/3’GAC motif found in r(CAG)exp hairpin structure were identified by using RNA binding studies and virtual screening/chemical similarity searching. Specifically, a benzylguanidine-containing small molecule was found to improve pre-mRNA alternative splicing of MBNL1-sensitive exons in cells expressing the toxic r(CAG)exp. The compound was identified by first studying the binding of RNA 1×1 nucleotide internal loops to small molecules known to have affinity for nucleic acids. Those studies identified 4',6-diamidino-2-phenylindole (DAPI) as a specific binder to RNAs with the 5’CAG/3’GAC motif. DAPI was then used as a query molecule in a shape- and chemistry alignment-based virtual screen to identify compounds with improved properties, which identified 4-guanidinophenyl 4-guanidinobenzoate as small molecule capable of improving pre-mRNA splicing defects associated with the r(CAG)exp-MBNL1 complex. This compound may facilitate the development of therapeutics to treat diseases caused by r(CAG)exp and could serve as a useful chemical tool to dissect the mechanisms of r(CAG)exp toxicity. The approach used in these studies, defining the small RNA motifs that bind known nucleic acid binders and then using virtual screening to optimize them for bioactivity, may be generally applicable for designing small molecules that target other RNAs in human genomic sequence. PMID:22252896

Optical Fluorescent Imaging to Monitor Temporal Effects of Microbubble-Mediated Ultrasound Therapy

PubMed Central

Sorace, Anna G.; Saini, Reshu; Rosenthal, Eben; Warram, Jason M.; Zinn, Kurt R.; Hoyt, Kenneth

2013-01-01

Microbubble-mediated ultrasound therapy can noninvasively enhance drug delivery to localized regions in the body. This technique can be beneficial in cancer therapy, but currently there are limitations to tracking the therapeutic effects. The purpose of this experiment was to investigate the potential of fluorescent imaging for monitoring the temporal effects of microbubble-mediated ultrasound therapy. Mice were implanted with 2LMP breast cancer cells. The animals underwent microbubble-mediated ultrasound therapy in the presence of Cy5.5 fluorescent-labeled IgG antibody (large molecule) or Cy5.5 dye (small molecule) and microbubble contrast agents. Control animals were administered fluorescent molecules only. Animals were transiently imaged in vivo at 1, 10, 30, and 60 min post therapy using a small animal optical imaging system. Tumors were excised and analyzed ex vivo. Tumors were homogenized and emulsion imaged for Cy5.5 fluorescence. Monitoring in vivo results showed significant influx of dye into the tumor (p < 0.05) using the small molecule, but not in the large molecule group (p > 0.05). However, after tumor emulsion, significantly higher dye concentration was detected in therapy group tumors for both small and large molecule groups in comparison to their control counterparts (p < 0.01). This paper explores a noninvasive optical imaging method for monitoring the effects of microbubble-mediated ultrasound therapy in a cancer model. It provides temporal information following the process of increasing extravasation of molecules into target tumors. PMID:23357902